Li-telomeres tse khutšoane le ho ruruha ho tlatsetsa ho lefu la tsoekere joang

Micrograph ea chromosomes ea motho e nang le li-telomeres (tse bontšitsoeng ka pinki). (Setšoantšo: Mary Armanios)

Li-Telomeres li pheta tatellano ea DNA e sirelletsang pheletso ea chromosomes. Ha 'mele o ntse o tsofala, hangata oa khutsufala. Maemong ana, lisele li felloa ke matla a ho arohana ka tsela e tloaelehileng ebe, qetellong, lia shoa. Ho khumama ha Telomere ho amana le mofetše, mafu a matšoafo le maloetse a mang a amanang le botsofe. Lefu la tsoekere, le amanang le botsofali, le ama motho a le mong ho ba baholo ho ba lilemo tse 60.

Phuputso e entsoeng ke bo-rasaense Univesithing ea Johns Hopkins, e hatisitsoeng koranteng ea PLoS One, e thehiloe tlhokomelong ea Mary Armanios, ea ileng a supa boteng ba kamano e hlakileng lipakeng tsa lefu la lefu la tsoekere le dyskeratosis (dyskeratosis congenital), lefu le sa tloaelehang la lefutso le bakiloeng ke tlolo ea ts'ebetso ea tlhokomelo. bolelele ba telomere. Ho bakuli ba nang le lefu la lefutso, lefutso le ho senyeha ha litho tse ngata pele ho nako hangata li bonoa.

“Congenital diskeratosis ke lefu le etsang hore batho ba tsofale pele ho nako. Re ne re tseba hore ts'oaetso ea lefu la tsoekere e eketsehile ka botsofaling, ka hona re khothaletsa hore ho ka ba le khokahano lipakeng tsa lits'oaetso tsa lefu la tsoekere le lefu la tsoekere, "ho boletse thuto Armanios, moprofesa ea amanang le oncology Univesithing ea Kanmel Cancer, Univesithi ea Johns Hopkins.

Ho bakuli ba nang le lefu la tsoekere, ha ho hlahisoe insulin e lekaneng, 'me lisele tsa bona ha li khone ho e sebelisa hantle, e lebisang tlolong ea molao oa tsoekere ea mali.

Armanios o ile a ithuta litoeba ka li-telomeres tse khutšoane le lisele tsa tsona tse hlahisang insulin. O fumane hore leha ho na le palo e kholo ea lisele tsa mmele oa beta tse shebahalang hantle, boemo ba tsoekere ea mali litonong tsena bo ne bo le holimo, 'me lisele li na le insulin tse peli tse tlase ho liphoofolo tsa sehlopha se laolang.

Armanios oa hlalosa: "Sena se tsamaisana le methati ea pele ea lefu la tsoekere ho batho, ha lisele li thatafalloa ke ho fumana insulin ka lebaka la tsoekere. "A litoeba tse joalo mehatong e mengata ea secretion insulinArmanios o re: "Ho tloha tlhahiso ea matla ka mitochondria ho ea ho calcium, lisele li sebetsa halofo ea tsona e tloaelehileng."

Lisele tsa beta tsa litoeba tse nang le li-telomeres tse khutšoane, bo-rasaense ba sibolotse mofuta oa p16 o amanang le botsofali le lefu la tsoekere. Ntle le moo, mefuta e mengata ea litsela tse hlokahalang bakeng sa ho boloka insulin, ho kenyelletsa le tsela e laolang ho tšoaea calcium e fetotsoe ho tsona. Sehlopheng sa taolo, ha ho liphoso tse joalo tse ileng tsa fumanoa.

Boithuto bo bong bo fetileng bo bontšitse hore bakuli ba nang le lefu la tsoekere ba ka ba le li-telomeres tse khutšoane, empa na lia eketseha kotsi ea lefu la tsoekere kapa ke ka lebaka la lefu lena, le ntseng le sa tsejoe.

“Ho tsofala ke sesosa se ka sehloohong sa lefu la tsoekere. Ntle le moo, lefutso la lelapa le bapala karolo ea bohlokoa haholo. Bolelele ba li-telomeres ke ntho ea lefa ebile e ka etsa hore batho ba tloaetse ho ba le lefu la tsoekere, "oa lumela Armanios.

Ho ipapisitsoe le mosebetsi ona, Armanios o phethela ka hore bolelele ba telomere bo ka sebetsa e le sehlahisoa sa lihlahisoa tsa lihlahisoa lefu la tsoekere. Patlisisong e tsoelang pele, bo-rasaense ba rera ho fumana hore na ho ka khoneha ho bolela esale pele kotsi ea ho ba le lefu lena ho latela bolelele ba telomere. ”

Li-telomeres tse khutšoane le ho ruruha ho tlatsetsa ho lefu la tsoekere joang

Li-telomeres tse khutšoane le ho ruruha ho tlatsetsa ho lefu la tsoekere joang

Hobaneng ha batho ba nang le mafura a mangata a ka mpeng ba eketsa ho hanyetsa insulin le menyetla ea bona ea lefu la tsoekere? Phepo e se nang phepo e ntle, mokhoa oa ho lula o lutse le khatello ea maikutlo li kenya letsoho ho theheng mafura a ka mpeng le ho eketseha ha tsoekere ea mali. Ho batho ba nang le mala, li-telomeres li khutsufala ho theosa le lilemo <5>, mme ho ka etsahala hore phokotso ea bona e mpefatse bothata ka ho hanyetsa insulin. Phuputsong ea Danish eo mafahla a 338 a neng a nkile karolo ho 'ona, ho ile ha fumaneha hore li-telomeres tse khutšoane ke li-bandbist tsa ho hanyetsa insulin haholo lilemong tse 12 tse tlang. Ka mafahla a mang le a mang, e mong oa bona eo li-telomeres tsa tsona li neng li le khuts'oanyane a bonts'a tekanyo e kholo ea insulin <6>.

Bo-rasaense ba bontšitse khafetsa kamano e pakeng tsa telomeres e khuts'oane le lefu la tsoekere. Li-telomeres tse khutšoane li eketsa kotsi ea ho ba le lefu la tsoekere: batho ba nang le lefu la nakoana la lefu la telomere ba na le monyetla oa ho ba le lefu lena ho feta bongata bohle. Lefu la tsoekere le qala hoseng 'me le tsoela pele ka potlako. Lithuto tsa Maindia, tseo ka mabaka a 'maloa li leng kotsing e kholo ea lefu la tsoekere, le tsona li fana ka litholoana tse nyahamisang. Mo India ea nang le li-telomeres tse khutšoane, monyetla oa ho ba le lefu la tsoekere ka lilemo tse hlano tse tlang o phahame habeli ho baemeli ba morabe o le mong o nang le li-telomeres tse telele tsa77. Tlhahlobo ea meta ea lithuto tse amang kakaretso ea batho ba fetang 7,000 e bonts'itse hore li-telomeres tse khutšoane liseleng tsa mali ke sesupo se ts'epahalang sa lefu la tsoekere la nakong e tlang.

Ha re tsebe feela ts'ebetso ea nts'etsopele ea lefu la tsoekere, empa re ka sheba le manyeme ho bona se etsahalang ho lona. Mary Armanios le basebetsi-mmoho ba bonts'itse hore litoeba, ha li-telomeres li fokotseha hohle 'meleng (bo-ramahlale ba fihletse sena ka phetoho ea liphatsa tsa lefutso), lisele tsa pancreatic beta li lahleheloa ke bokhoni ba tsona ba ho hlahisa insulin <9>. Lisele tsa stem ka har'a manyeme lia tsofala, li-telomeres tsa tsona li se li le khuts'oane haholo, 'me ha ba sa khona ho khutlisa mefuta ea lisele tsa beta tse ikarabellang bakeng sa tlhahiso ea insulin le taolo ea boemo ba eona. Lisele tsena lia shoa. Mme mofuta oa lefu la tsoekere o theohela khoebong. Ka lefu la tsoekere la mofuta oa II le tloaelehileng, lisele tsa beta ha li bolaee, empa ts'ebetso ea tsona ha e na matla. Ka hona, ntlheng ena, hape, li-telomeres tse khutšoane ho manyeme li ka bapala karolo.

Ho motho ea phetseng hantle, borokho bo tsoang ho mafura a ka mpeng ho ea ho lefu la tsoekere bo ka beoa ke motsoalle oa rona oa khale - ts'oaetso e sa foleng. Mafura a ka mpeng a kenya letsoho haholo kholisong ea ho ruruha ho feta, ho re, mafura lethekeng. Lisele tsa "Adipose" tsa lisele tsa pele tse ka fokolisang lisele tsa tsamaiso ea 'mele ea ho itšireletsa mafung, li li etsa hore li fokotsehe le ho senya li-telomeres tsa tsona. Joalokaha u hopola, lisele tsa khale, le tsona lia amoheloa ho romella matšoao a sa emiseng a tsosang ho ruruha hoa mmele - sekala se lonya se fumanoa.

Haeba u na le mafura a mangata ka mpeng, u lokela ho ba hlokolosi ho itšireletsa khahlanong le ho ruruha ho sa feleng, telomeres e khutšoane le metabolic syndrome. Empa pele o qeta ho ja ho tlosa mafura a ka mpeng, bala khaolo ena ho fihlela qetellong: u ka nka qeto ea hore lijo li mpefala le ho feta. Se ke oa tšoenyeha: re tla u fa mekhoa e meng ea ho ntlafatsa metabolism ea hau.

Abstract ea sengoloa sa mahlale mabapi le bongaka le tlhokomelo ea bophelo bo botle, mongoli oa mosebetsi oa mahlale - Brailova Nataliya Vasilievna, Dudinskaya Ekaterina Nailevna, Tkacheva Olga Nikolaevna, Shestakova Marina Vladimirovna, Strazhesko Irina Dmitrievna, Akasheva Dariga Uaydinichna, Plodhvaina Odachina Anatolyevich

Morero oa thuto e ne e le ho ithuta kamano ea ho ruruha ho sa foleng, khatello ea oxidative, le biel ea telomere ho batho ba nang le mofuta oa lefu la tsoekere la 2 lefu la tsoekere. Lintho tse bonahalang le mekhoa. Phuputso e kenyelelitse bakuli ba 50 ba nang le lefu la tsoekere la mofuta oa 2 ntle le lipontšo tsa kliniki ea lefu la pelo (CVD) le batho ba 139 sehlopheng sa taolo. Boemo ba metabolism ea carbohydrate, tekanyo ea khatello ea oxidative (MDA malondialdehyde) le ho ruruha ho sa foleng (fibrinogen, protheine ea C-reactive CRP, li-interleukin-6 IL-6) li ile tsa hlahlojoa, bolelele ba li-lymphocytic telomeres le ts'ebetso ea telomerase li lekantsoe. Liphetho Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, bolelele ba telomere bo ne bo le bokhuts'oane (p = 0.031), ts'ebetso ea telomerase e ne e le tlase (p = 0.039), 'me boemo ba tšoaetso (CRP le fibrinogen) bo ne bo phahame ho feta sehlopheng sa taolo. Bakuli bohle ba ne ba arotsoe ka bolelele ba telomere. Har'a bakuli ba nang le T2DM, CRP le fiberrinogen maemo a ne a phahame ho batho ka bomong ba nang le li-telomeres tse khutšoane (p = 0.02). Ha ho bapisoa lihlopha le li-telomeres tse “telele”, ha ho liphapang tse fumanoeng maemong a CRP (p = 0.93). Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 le ts'ebetso ea "tlase" telomerase, bothata ba ho ruruha ho sa foleng bo ne bo le boholo haholo. Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, kamano e fumanoe pakeng tsa bolelele ba telomere le boemo ba CRP (r = -0.40, p = 0.004). Qeto Ho ruruha ho sa feleng le ho tsofala ha sele ho bakuli ba nang le lefu la tsoekere la 2 ho boleloa haholo ho feta taolong. Leha ho le joalo, ho bakuli ba nang le li-telomeres tse “telele”, matšoao a tšoaetso e sa foleng a ne a sa fapana haholo le a batho ba phetseng hantle. Mohlomong li-telomere tse "telele" li sireletsa bakuli ba nang le T2DM litlamorao tse mpe tsa ho ruruha ho sa feleng.

Bolelele ba Telomere, ts'ebetso ea telomerase le mekhoa e fetoha ho bakuli ba mofuta oa 2 lefu la tsoekere

Sepheo. Ho ithuta ho tloaelana le ho ruruha ho sa feleng, khatello ea oxidative le telomere biology ho batho ba nang le mofuta oa 2 lefu la tsoekere (T2DM). Lintho tse bonahalang le mekhoa. Bakuli ba 50 kaofela ba nang le T2D le ba se nang lefu la pelo (CVD) le batho ba 139 ba tsoang sehlopheng sa taolo ba kenyelelitsoe thutong. Lithuto tsohle li ile tsa lekanyetsoa metabolism ea carbohydrate, khatello ea oxidative (malondialdehyde (MDA)), ho ruruha (C-reactive protein CRP, fibrinogen, interleukin-6), lymphocyte telomere bolelele, mosebetsi oa telomerase. Liphetho Ho bakuli ba lefu la tsoekere li-telomeres li ne li le khuts'oane ho feta lits'ebetsong (9.59 ± 0.54 le 9.76 ± 0.47, p = 0.031), ts'ebetso ea telomerase e ne e le tlase (0.47 ± 0.40 le 0.62 ± 0.36, p = 0.039), ho ruruha (CRP, fibrinogen e phahameng) e ne e phahame . Bakuli bohle ba ne ba le div> telomere bolelele. Ka T2DM sehlopha CRP e ne e phahame ho bakuli ba nang le li-telomeres tse “khutšoane” (7.39 ± 1.47 le 3.59 ± 0.58 mg / L, p = 0.02). Ha ho na phapang e kholo maemong a ho ruruha ho sa feleng le khatello ea oksijene sehlopheng sa li-telomeres tsa nako e telele: CRP 3.59 ± 0.58 le 3.66 ± 0.50 mg / L (p = 0.93), MDA 2.81 ± 0.78 le 3.24 ± 0.78 mmol / l ( p = 0.08). Bakuli ba lefu la tsoekere sehlopheng sa "telomeres" sa nakoana "ba ne ba na le ts'oaetso e sa foleng: CRP 7.39 ± 1.47 le 4.03 ± 0.62 mg / L (p = 0.046), fibrinogen e eketsehang, 0.371 le 0.159 (p = 0.022). Bakuli bohle e ne e le karolo ea div> telomerase. Tekanyo ea ho ruruha ho sa foleng e ne e le kholo ho T2DM le ts'ebetso ea "tlase" ea telomerase. Ho ne ho na le kamano pakeng tsa bolelele ba telomere le CRP ho bakuli ba T2DM (r = -0.40, p = 0.004). Liphetho. Ho ruruha ho sa feleng le ho ruruha ha sele ho ne ho boleloa haholoanyane ho bakuli ba nang le T2DM. Leha ho le joalo, ho sa tsotellehe lefu la tsoekere, matšoao a ho ruruha ho sa foleng a ne a le manyane ho bakuli ba nang le li-telomeres tse "telele" ha li bapisoa le batho ba phetseng hantle. Mohlomong li-telomeres tse telele li sireletsa bakuli ba lefu la tsoekere khaellong e mpe ea ts'oaetso e sa foleng.

Lingoloa tsa saense e buang ka "bolelele ba Telomere, telomerase shughuli, le mekhoa ea liphetoho tsa bona ho mokuli ea nang le lefu la tsoekere la mofuta oa 2"

Bolelele ba Telomere, ts'ebetso ea telomerase le mekhoa ea liphetoho tsa bona ho mokuli ea nang le lefu la tsoekere la mofuta oa 2

Ph.D. N.V. BRAYLOVA1 *, Ph.D. E.N. DUDINSKAYA1, MD O.N. TKACHEVA1, setho se tsamaellanang RAS M.V. SHESTAKOVA2, Ph.D. I.D. STRAZHESKO1, mokhethoa oa lithuto tsa bongaka tsa bongaka D.U. AKASHEV1, E.V. PLOKHOVA1, V.S. Pykhtina1, V.A. VYGODIN1, prof. S.A. MOJALEFA1

1 FSBI "Setsi sa Patlo ea Naha bakeng sa Phekolo ea Thibelo", Moscow, Russia, 2 FSBI "Setsi sa Patlisiso ea Endocrinological" sa Lefapha la Bophelo la Russia, Moscow, Russia

Morero oa thuto e ne e le ho ithuta kamano ea ho ruruha ho sa foleng, khatello ea oxidative, le biel ea telomere ho batho ba nang le mofuta oa lefu la tsoekere la 2 lefu la tsoekere.

Lintho tse bonahalang le mekhoa. Phuputso e kenyelelitse bakuli ba 50 ba nang le lefu la tsoekere la mofuta oa 2 ntle le lipontšo tsa kliniki ea lefu la pelo (CVD) le batho ba 139 sehlopheng sa taolo. Boemo ba metabolism ea carbohydrate, tekanyo ea khatello ea oxidative (malondialdehyde - MDA) le ho ruruha ho sa foleng (fibrinogen, protheine ea C-reactive - CRP, li-interleukin-6 - IL-6) li ile tsa hlahlojoa, bolelele ba li-lymphocyte telomeres le telomerase e lekantsoe.

Liphetho Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, bolelele ba telomere bo ne bo le bokhuts'oane (p = 0.031), ts'ebetso ea telomerase e ne e le tlase (p = 0.039), 'me boemo ba tšoaetso (CRP le fibrinogen) bo ne bo phahame ho feta sehlopheng sa taolo. Bakuli bohle ba ne ba arotsoe ka bolelele ba telomere. Har'a bakuli ba nang le T2DM, CRP le fiberrinogen maemo a ne a phahame ho batho ka bomong ba nang le li-telomeres tse khutšoane (p = 0.02). Ha ho bapisoa lihlopha le li-telomeres tse “telele”, ha ho liphapang tse fumanoeng maemong a CRP (p = 0.93). Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 le ts'ebetso ea "tlase" telomerase, bothata ba ho ruruha ho sa foleng bo ne bo le boholo haholo. Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, kamano e fumanoe pakeng tsa bolelele ba telomere le boemo ba CRP (r = -0.40, p = 0.004).

Qeto Ho ruruha ho sa feleng le ho tsofala ha sele ho bakuli ba nang le lefu la tsoekere la 2 ho boleloa haholo ho feta taolong. Leha ho le joalo, ho bakuli ba nang le li-telomeres tse “telele”, matšoao a tšoaetso e sa foleng a ne a sa fapana haholo le a batho ba phetseng hantle. Mohlomong li-telomere tse "telele" li sireletsa bakuli ba nang le T2DM litlamorao tse mpe tsa ho ruruha ho sa feleng.

Mantsoe a bohlokoa: bolelele ba telomere, ts'ebetso ea telomerase, lefu la tsoekere, ho ruruha ho sa foleng, khatello ea oxidative.

Bolelele ba Telomere, ts'ebetso ea telomerase le mekhoa e fetoha ho bakuli ba mofuta oa 2 lefu la tsoekere

N.V. BRAILOVA1, E.N. DUDINSKAYA1, O.N. TKACHEVA1, M.V. SHESTAKOVA2, I.D. STRAZHESKO1, D.U. AKASHEVA1, E.V. PLOCHOVA1, V.S. PYKHTINA1, V.A. VYGODIN1, S.A. BOYTSOV1

'Setsi sa Lipatlisiso sa Sechaba sa Bongaka ba Thibelo, Moscow, Russia, Setsi sa Patlisiso sa 2 sa Endocrinology, Moscow, Russia

Sepheo. Ho ithuta ho tloaelana le ho ruruha ho sa feleng, khatello ea oxidative le telomere biology ho batho ba nang le mofuta oa 2 lefu la tsoekere (T2DM).

Lintho tse bonahalang le mekhoa. Bakuli ba 50 kaofela ba nang le T2D le ba se nang lefu la pelo (CVD) le batho ba 139 ba tsoang sehlopheng sa taolo ba kenyelelitsoe thutong. Lithuto tsohle li ile tsa lekanyetsoa metabolism ea carbohydrate, sehlopha sa li-oxelomeres: CRP 3.59 ± 0.58 le 3.66 ± 0.50 mg / L (p = 0.93), MDA 2.81 ± 0.78 le 3.24 ± 0.78 mmol / l (p = 0.08). Bakuli ba lefu la tsoekere sehlopheng sa "telomeres" sa nakoana "ba ne ba na le ts'oaetso e sa foleng: CRP 7.39 ± 1.47 le 4.03 ± 0.62 mg / L (p = 0.046), fibrinogen e eketsehang, 0.371 le 0.159 (p = 0.022). Bakuli bohle ba ne ba le div>

Liphetho. Ho ruruha ho sa feleng le ho ruruha ha sele ho ne ho boleloa haholoanyane ho bakuli ba nang le T2DM. Leha ho le joalo, ho sa tsotellehe lefu la tsoekere, matšoao a ho ruruha ho sa foleng a ne a le manyane ho bakuli ba nang le li-telomeres tse "telele" ha li bapisoa le batho ba phetseng hantle. Mohlomong li-telomeres tse telele li sireletsa bakuli ba lefu la tsoekere khaellong e mpe ea ts'oaetso e sa foleng.

Mantsoe a bohlokoa: bolelele ba telomere, mosebetsi oa telomerase, lefu la tsoekere, ho ruruha ho sa foleng, khatello ea oxidative.

Khatello ea kelello le ho ruruha ho sa feleng e le motheo oa botsofali

Lefu la tsoekere mellitus (DM) le tsamaisoa le liphetoho tse potlakileng methapong ea mali, e e etsang sesosa sa pele sa lefu la pelo le lefu la lefu. Khokahano ea data ea bohlokoa

liphetoho - hyperglycemia, ho hanyetsa insulin, ho bokella lihlahisoa tsa ho qetela tsa glycation (CNG). Hyperinsulinemia le hyperglycemia, hammoho le botsofali ba 'mele, li kenya ts'ebetsong lits'ebetso tsa ho ruruha ho sa feleng le khatello ea maikutlo. Mmeleng o tsofetseng, joalo ka an

boemo bo tlase ba mokuli ea nang le lefu la tsoekere, boemo ba matšoao a fapaneng a ts'oaetso bo eketsa protheine ea C-reactive (CRP), IL-18, TNF-a ("ho ruruha"), e eketsa ts'ebetso ea lipid peroxidation ka ho etsoa ha malondialdehyde (MDA) le mefuta ea oksijene e sebetsang (ROS) . Sena sohle se lebisa ho kopantsoeng ha protheine e sa sebetseng, apoptosis ea sele le nts'etsopele ea litsamaiso tse mpefatsang.

Biology ea li-telomeres ho batho ba nang le lefu la tsoekere la mofuta oa 2

Le leng la mabaka a tekanyetso e fapaneng ea botsofe ba methapo ho bakuli ba nang le lefu la tsoekere la 2 ke "tšireletso ea liphatsa tsa lefutso" e fapaneng le ea ho pepesetsoa mabaka a kantle. Bolelele ba telomere le mosebetsi oa telomerase li ka nka karolo ea lipalo tsa liphatsa tsa lefutso tsa methapo ea mali. Li-Telomeres ke likarolo tsa "molek'hule tsa DNA tse tsamaeang butle li khutsufatsoa butle-butle ka karolo e 'ngoe le e' ngoe ea sele. Hang ha bolelele ba DNA ea telomeric bo theoha ka mokhoa o kotsi, P53 / P21, botsofaling ba seleng, e bolokoa ha e ntse e boloka tšebetso ea eona ea metabolic. Ho na le bopaki ba hore bolelele ba li-telomeres ho leukocytes bo bontša bolelele ba li-telomeres liseleng tsa stem mme li lekana le bolelele ba tsona liseleng tsa progenitor tsa endothelial, tse re lumellang ho nahana ka paramente ena e le biomarker ea botsofaling ba methapo. Matšoao a pele a bokhutšoanyane ba telomere ho batho ba nang le lefu la tsoekere la mofuta oa 2 le mamello ea tsoekere e fumanoeng a fumanoe. Ho khutsufatsa ha Telomere ho ka amahanngoa le nts'etsopele ea T2DM, CVD le ho ruruha ha methapo.

Letšoao la bobeli la liphatsa tsa lefutso le tsoaloang e ka ba ts'ebetso ea telomerase. Telomerase ke enzyme e eketsang tatellano e ikhethang ea ho pheta-pheta ha DNA ho 3'-pheletso ea ketane ea DNA mme e kenyelletsa telomerase reverse transcriptase (TERT) le telomerase RNA (TERC). Liseleng tse ling tse ngata, ts'ebetso ea telomerase e tlase haholo. Le ha telomerase e sa bapala karolo ea bohlokoa ho telomere bolelele homeostasis botsofaling, ho lumeloa hore enzyme ena e na le mesebetsi ea bohlokoa eo e seng ea telomere ho fokotsa apoptosis, control proliferation ea cell, le ts'ebetso ea mitochondrial liseleng tsa batho.

Karolo ea ho ruruha ho sa feleng le oxidative

khatello ea maikutlo maemong a phetoho ea bolelele ba telomere

telomerase ho batho ba nang le lefu la tsoekere la mofuta oa 2

Lisosa tsa mantlha tsa methapo ea methapo ea methapo e amanang le botsofe maemong a methapo ea methapo e nkuoa e le khatello ea maikutlo le ts'oaetso e sa foleng, e bakang khutsufatso e sa phetseng ea DNA. Li-teleomeres li tebile

Li ikarabella bakeng sa tšenyo ea oxidative ea molek'hule ea DNA. In vitro ROS e fokotsa litaba tsa protheine ea nyutlelie ea hTERT liseleng tsa endothelial, ka hona, ketsahalo ea telomerase. Telomerase e ka sireletsa lisele tse tšoeu tsa mali ho tsoa likhatellong tsa oxidative ntle le ho ama bolelele ba li-telomeres. Ts'ebetso e eketsehang ea ts'oaetso e potlakisa ho khutsufatsoa ha li-telomeres ka bobeli ka lebaka la ts'ebetso ea ho ata ha lisele, le ka lebaka la tokollo ea ROS. Phokotso e tsoelang pele ea li-telomere le keketseho ea nako ea T2DM li kanna tsa amahanngoa le ho ruruha ho sa feleng le khatello ea maikutlo. Kamano pakeng tsa ts'ebetso ea telomerase le ho ruruha ho sa foleng li tsoakane. Ho ruruha ho sa feleng qalong ka mekhoa e mengata e tšoaeang (e kenyang NF-kB, protheine kinase C kapa Akt kinase) ka phosphorylation kapa transcript ea hTERT e ka kenya telomerase, eo,

Tlhahisoleseling mabapi le bangoli:

Brailova Natalia Vasilievna - Ph.D. Dep.Boithuto ba ho tsofala le thibelo ea mafu a amanang le lilemo tsa Setsi sa Patlo ea Naha sa kalafo ea kalafo, Moscow, Russia, imeile: [email protected],

Dudinskaya Ekaterina Nailevna - moemeli oa saense ea bongaka, mothusi ea phahameng oa mahlale Dep. Boithuto ba ho tsofala le thibelo ea maloetse a amanang le lilemo tsa Federal State Budgetary Institution "Setsi sa Patlo ea Naha bakeng sa Thibelo ea Thibelo", Moscow, Russia,

Tkacheva Olga Nikolaevna - MD, prof., Hands. Dep. ho ithuta mekhoa ea botsofali le thibelo ea mafu a amanang le lilemo tsa FSBI State Research Center bakeng sa Phekolo ea Thibelo, Moscow, Russia, Shestakova Marina Vladimirovna - setho se lumellanang. RAS, Motsamaisi oa Setheo sa lefu la tsoekere, Motlatsi mohloa Mosebetsi oa saense oa Federal State Budgetary Institution "Setsi sa Saense sa Endocrinological", Moscow, Russia, Strazhesko Irina Dmitrievna - moemeli oa saense ea bongaka, mofuputsi ea phahameng Dep. Boithuto ba ho tsofala le thibelo ea maloetse a amanang le lilemo tsa Federal State Budgetary Institution "Setsi sa Patlo ea Naha bakeng sa Thibelo ea Thibelo", Moscow, Russia,

Akasheva Dariga Uaydinichna - moemeli oa saense ea bongaka, mofuputsi ea phahameng Dep. Boithuto ba ho tsofala le thibelo ea maloetse a amanang le lilemo tsa Federal State Budgetary Institution "Setsi sa Patlo ea Naha bakeng sa Thibelo ea Thibelo", Moscow, Russia,

Plokhova Ekaterina Vladimirovna - moemeli oa saense ea bongaka, mofuputsi ea phahameng Dep. Boithuto ba ho tsofala le thibelo ea maloetse a amanang le lilemo tsa Federal State Budgetary Institution "Setsi sa Patlo ea Naha bakeng sa Thibelo ea Thibelo", Moscow, Russia,

Pykhtina Valentina Sergeevna - lab. Dep. Boithuto ba ho tsofala le thibelo ea maloetse a amanang le lilemo tsa Federal State Budgetary Institution "Setsi sa Patlo ea Naha bakeng sa Thibelo ea Thibelo", Moscow, Russia,

Vygodin Vladimir Anatolyevich - mofuputsi ea phahameng lab. biostatistics Federal State Budgetary Institution "Setsi sa Patlo ea Naha bakeng sa Thibelo ea Thibelo", Moscow, Russia, Sergey Anatolyevich Boytsov - MD, moprofesa, matsoho. Dep. Cardiology le Molecular Genetics, Motsamaisi, Setsi sa Patlisiso ea Naha bakeng sa Thibelo ea Thibelo ea Ts'ireletso, Moscow, Russia

Piano, e lekana le ho khutsufatsa ho potlakileng ha mehato ea 'mele. Leha ho le joalo, mehatong ea morao ea ho ruruha, ts'ebetso ea telomerase ea fokotseha, e lebisang ho khutsufatso ea li-telomeres.

Morero oa thuto e ne e le ho ithuta kamano ea ho ruruha ho sa feleng le khatello ea maikutlo le "biology" ea telomere ho batho ba nang le lefu la tsoekere la mofuta oa 2.

Lintho tse bonahalang le mekhoa

Phuputso e le 'ngoe e kenyelletsa bakuli ba nang le lefu la tsoekere la mofuta oa 2 ba ileng ba ngola tlhahlobo ea kantle ho Setsi sa Patlisiso sa Mahlale sa Federal State Budget sa Saense ka 2012-2013. Sehlopha se ka sehloohong se ne se e-na le bakuli ba lilemo tse 45 ho isa ho tse 75 ba nang le lefu le sa feteng likhoeli tse 12 le litaba tsa HbA1c tsa 6.5 ho isa 9,0%. Sehlopha sa taolo se ne se kenyelletsa batho ba se nang T2DM ba neng ba se na lipontšo tsa bongaka tsa CVD, ba ileng ba leba setsing bakeng sa tlhabollo ea thibelo.

Litekanyetso tsa ho kenyelletsa: mofuta oa 1 lefu la tsoekere le mefuta e meng e ikhethang ea lefu la tsoekere, khatello ea methapo ea methapo (khatello ea mali) (khatello ea mali> proliferative diabetesic retinopathy, lefu la liphio le sa foleng la methapo ea 3b, 4 le 5), CVD (lefu la pelo le sa foleng, limaraka II - IV (NYHA), lefu la pelo le sa foleng), ho nyeleha ho sa foleng ha sebete, mofets'e, ho ima, le ho nyeka.

Bakuli bohle ba saena tumello e nang le tsebo ea ho nka karolo thutong. Setifikeiti sa thuto se amohetsoe ke komiti ea boitšoaro ea lehae ea FSBI GNITsPM ea Lekala la Bophelo la Russia. Protocol ea seboka sa LEK No. 8 ea 11.29.11.

Nakong ea tlhahlobo, bakuli bohle ba hlahlobeloa tlhahlobo e tloaelehileng ea bongaka: ho nka nalane, tlhahlobo ea bongaka, ho kenyelletsa tekanyo ea boima ba 'mele le bophahamo ka lipalo tsa index ea' mele (BMI), tekanyo ea systolic (SBP) le khatello ea mali ea diastolic (DBP) sesebelisoa se lekantsoeng. o sebelisa mokokotlo oa mahetla (HEM-7200 M3, Omron Healthcare, Japan). Khatello ea mali e lekantsoe kamora phomolo ea metsotso e 10 letsohong le letona sebakeng sa ho lula makhetlo a 3 kamora metsotso e 2, tekanyo ea litekanyo tse tharo e kenyelelitsoe ho tlhahlobo. Madi a nkiloe bakeng sa liteko tsa laboratori (tsa bongaka le tsa biochemical), ECG e tlalehiloe, 'me tlhahlobo ea boikoetliso ba' mele e ile ea etsoa tlhahlobisong ea treadmill e sebelisa protocol ea BRUCE (Intertrack, SCHILLER). Ho bakuli ba 250 ba hlahlobiloeng, 189 ba fihletse maemo a ho kenyelletsa. Boemo ba metabolism ea carbohydrate bo ile ba hlahlojoa ho bona kaofela, bolelele ba telomere le ts'ebetso ea telomerase bo ile ba beoa, le ho teba ha khatello ea oxidative le ts'oaetso e sa foleng li tlalehiloe.

Carbohydrate metabolism

Ts'oaetso ea glucose ea plasma e ile ea khethoa ke mokhoa oa glucose oxidase ho mohlahlobi oa SAPPHIRE-400 o sebelisa li-diagnostic tsa DiaSys. Boemo ba HbA1c bo tlalehiloe ke chromatography ea metsi ho mohlahlobi oa Sapphire 400 (Niigata Mechatronics, Japan) ho latela ts'ebetso e tloaelehileng ea moetsi.

Tekanyo ea bolelele ba Telomere

Tekanyo ea bolelele bo lekanang ba li-telomeres tsa peripheral lymphocyte e ne e etsoa ho genomic DNA. Nakong ea tlhahlobo ea PCR ea 'nete, tekanyo ea DNA e nang le tatellano ea telomeric ho genome e ile ea hakangoa. Ka ho tšoanang, PCR ea nako ea nnete e ile ea etsoa kopi e le 'ngoe ea DNA ea genomic. Re tlohile ka tekanyo ea palo ea litekanyetso tsa li-telomeric le likopi tse le 'ngoe ho ea bolelele ba li-telomeres.

Tekanyo ea mosebetsi oa telomerase

Ho khetholla ts'ebetso ea telomerase, ho ile ha sebelisoa mokhoa o nang le liphetoho tse itseng. Ts'ebetso ea enzyme e ile ea etsoa lipatlisiso karolong e khethiloeng ea monocytic ea lisele tsa mali (hoo e ka bang lisele tse 10 000 ka tlhahlobo). Lisele tsa Monocyte li ile tsa kenngoa ka sekhukhu ka sesepa se bonolo, se arola nko. Karabelo ea telomerase polymerase e ile ea etsoa ka ho hula; lihlahisoa tse fumanoeng li ile tsa matlafatsoa ke PCR ea nako ea nnete. Palo ea lihlahisoa tsa telomerase reaction li lekana le ts'ebetso ea telomerase (Mastercyste amplifier (Eppendorf, Jeremane).

Tlhahlobo ea Khatello ea Khatello ea Kelello

Ho lekola botebo ba khatello ea ts'oaetso ea oxidative, khatello ea MDA e ile ea ithutoa ke mokhoa oa chemiluminescence o itšetlehileng ka luminol maling ohle.

Tlhahlobo ea ho ruruha ho sa foleng

Ho hlahloba botebo ba ts'oaetso e sa foleng, re ithutile ho hlaseloa ha protrinogen, e leng protheine ea C-reactive haholo (CRP) (mokhoa oa immunoturbodimetric o sebelisang tlhahlobo ea SAPPHIRE-400), IL-6 (mokhoa oa immuno-enzyme).

Ho tsamaisana le litekanyetso tsa biomedical ethics

Boithuto bona bo entsoe ho latela litekanyetso tse ntle tsa Clinical Exercise le melaoana ea Phatlalatso ea Helsinki. Setifikeiti sa thuto se amohetsoe ke Likomiti tsa Boitšoaro ba litsi tsohle tsa kliniki tse nkang karolo. Pele ho kenyelletsoa lipatlisiso

Barupeluoa bohle ba fumane tumello e ngotsoeng.

Re sebelisitse sethala sa mananeo a sebelisitsoeng a lipalo SAS 9.1 (Sisteme Analysis System, SAS Institute Inc., USA). Lintlha tsohle li ile tsa kenngoa ka har'a processor ea tabular, ka mor'a moo ho ile ha etsoa tlhahlobo ea tlhahlobo ho bona liphoso tsa ho kenyelletsa le boleng bo lahlehileng. Bakeng sa litekanyetso tse ngata, liteko tsa asymmetry le kurtosis li ile tsa sebelisoa, tse ileng tsa senola phepelo e tloaelehileng ea litekanyetso tse ngata. Lintlha tsa bohlokoa li hlahisoa e le li-boleng tse mpe le ho kheloha ho tloaelehileng (M ± SD). Boleng ba boleng ba liparamente tsa bongaka bo ne bo bapisoa ka lihlopha tse peli li sebelisa tlhahlobo e le 'ngoe bakeng sa li-variables tse tsoelang pele le sekhahla sa x2 bakeng sa mefuta e fapaneng. Bakeng sa matšoao a khafetsa, mokhoa o fetotsoeng oa Moithuti ¿o sebelisitsoe o nahana ka phetoho ea Fcsher arcsin. Ho khetholla tekanyo ea kamano ea methapo lipakeng tsa paramente, ho ile ha etsoa tlhahlobo ea khokahano (Lipolelo tsa boemo ba puo). Ho lekola likamano tse ikemetseng lipakeng tsa litekanyetso, ho lekantsoe li-multidimensional regression equation le tlhaiso-leseling ea mela e mengata e sebelisitsoeng. Kamora ho lekanya bolelele ba telomere, karohano e eketsehileng ea bakuli ka bongata e entsoe ho latela boleng ba paramente. Sehlopha sa maemo a pele se ne se kenyelletsa bakuli ba nang le bolelele bo bokhutšoanyane ba telomere: ho tloha ka boleng bo tlase sehlopheng ka kakaretso ho ea moeling oa mohala oa pele (ke ka tlase ho 25% ea moeli oa kabo). Sehlopha sa maemo a bobeli se ne se kenyelletsa bakuli ba bolelele ba telomere ho tloha ho ajoa mahareng ho isa mekheng e tlaase. Sehlopha sa maemo a boraro se kenyelelitse bakuli ba bolelele ba telomere ho tloha phetisong ea mahareng ho isa ho 75% ea moeli oa kabo. Batho ba bolelele bo boholo ba telomere, e leng karolo e kaholimo ea kabo, ba abetsoe sehlopha sa maemo a bone. The null hypothesis e ile ea haneloa ho p i Ha ke khone ho fumana seo u se hlokang? Leka ts'ebeletso ea khetho ea lingoliloeng.

Ka kakaretso bakuli ba 189 (banna ba 64 le basali ba 125) ba kenyelelitsoe thutong eo, e neng e kopantsoe ka lihlopha tse peli: le T2DM (i = 50) ntle le lefu la tsoekere (i = 139). Nako ea T2DM e ne e le lilemo tse 0.9 + 0.089. Karolelano ea lilemo tsa bakuli ba nang le lefu la tsoekere la mofuta oa 2 e ne e le lilemo tsa 58.4 ± 7.9, mme sehlopha sa taolo - lilemo tse 57.45 + 8.14 (p = 0.48). Ka sehlopha sa SD2, SBP e ne e le 131.76 + 14.7 mm Hg, mme sehlopheng sa taolo - 127.78 + 16.5 mm Hg. (p = 0.13). Boemo ba MDA sehlopheng sa T2DM e ne e le 3.193 + 0.98 μmol / L, 'me sehlopheng sa taolo e ne e le 3.195 + 0.82 μmol / L (p = 0.98). Tekanyo e tloaelehileng ea IL-6 sehlopheng sa T2DM e ne e le 3.37 + 1.14 pg / ml, sehlopheng sa taolo e ne e le 5.07 + 0.87 pg / ml (p = 0.27).

Sehlopheng sa lefu la tsoekere, karolo ea banna e ne e phahame ho feta sehlopheng sa batho ba phetseng hantle (46% bapisoa le 29%) (p = 0.013). Karolelano ea banna / basali ka har'a sehlopha sa T2DM e ne e le 46/54% bapisoa le 29/71% sehlopheng sa taolo (^ = 0.013). BMI ea bakuli ba nang le lefu la tsoekere la mofuta oa 2 e ne e phahame haholo ho feta ho batho ba phetseng hantle: 30.28 42 5.42 bapisoa le 2768 ± 4.60 kg / m2 (p = 0.002). DBP sehlopheng sa T2DM e ne e le 83.02 ± 11.3 mm Hg. bapisoa 78.6 ± 9.3 mmHg sehlopheng sa taolo (p = 0.015). Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, bolelele ba li-telomeres tsa lymphocytic bo ne bo le bokhutšoanyane haholo (p = 0.031), le ts'ebetso ea telomerase e ne e le tlase haholo (p = 0.039) ho feta ho batho ba phetseng hantle. Sehlopheng sa T2DM, boemo ba "glucose glucose" (GPN) bo potlakileng le HbA1c bo ne bo phahame haholo ho feta sehlopheng sa taolo (p. Ha ke fumane seo u se hlokang? Leka ts'ebeletso ea khetho ea lingoliloeng.

mer 9.59 + 0.54 9.76 + 0.47 0.031

Ts'ebetso ea Telomerase 0.47 + 0.40 0.62 + 0.36 0.039

MDA, μmol / L 3.19 + 0.98 3.20 + 0.82 0.98

IL-6, pg / ml 3.37 + 1.14 5.07 + 0.87 0.27

CRP, mg / L 6.34 + 1.06 3.82 + 0.41 0.031

Fibrinogen, g / l 3.57 + 0.87 3.41 + 0.54 0.23

fibrinogen 0,30 + 0,04 0,11 + 0,03 0,004

Tafole ea 2. Matšoao a metabolism ea carbohydrate metabolism, khatello ea oxidative, ho ruruha ho sa foleng, bolelele ba telomere le telomerase, ho latela boteng ba T2DM

SD2 + ("= 50) ___ SD2- (" = 139)

Litekanyo tse telele tsa 'mele ("= 15) litekanyo tse khutšoane tsa' mele (" = 35) Litekanyo tse telele tsa 'mele ("= 76) litekanyo tse khutšoane tsa' mele (" = 63) P

HbA1c,% 11.54 + 3.57 13.48 + 3.24 0.072 10.98 + 1.83 11.59 + 2.03 0.075

GPN, mmol / L 0.83 + 0.13 0.95 + 0.17 0.02 0.76 + 0.16 0.78 + 0.14 0.59

MDA, μmol / L 2.81 + 0.78 3.35 + 1.04 0.09 3.24 + 0.78 3.14 + 0.87 0.58

CRP, mg / L 3.59 + 0.58 7.39 + 1.47 0.02 3.66 + 0.50 4.07 + 0.68 0.63

Fibrinogen, g / l 3.39 + 0.55 3.70 + 0.91 0.15 3.38 + 0.53 3.44 + 0.55 0.50

Ho ba teng ha fibrinogen e ntseng e eketseha 0.143 0.371 0,09 0,069 0,159 0.09

IL-6, pg / ml 5.95 + 3.89 2.43 + 0.51 0.39 5.70 + 1.31 4.41 + 1.08 0.45

Ts'ebetso ea Telomerase 0.51 + 0.09 0.47 + 0.08 0.78 0.60 + 0.05 0.66 + 0.07 0.42

Ts'ebetso ea "Low" telomerase 0.417 0.710 0.09 0.512 0.474 0.73

Lethathamo la 3. Matšoao a khatello ea ts'oaetso ea oxidative, ts'oaetso e sa foleng le ts'ebetso ea telomerase ho latela bolelele ba li-telomeres.

Li-telomeres tse telele li khutšoane

Paramente SD2 + ("= 15) SD2- (" = 76) P SD2 + ("= 35) SD2- (" = 63) P

MDA, μmol / L 2.81 + 0.78 3.24 + 0.78 0.08 3.35 + 1.04 3.14 + 0.87 0.35

CRP, mg / L 3.59 + 0.58 3.66 + 0.50 0.93 7.39 + 1.47 4.03 + 0.62 0.046

Fibrinogen, g / l 3.39 + 0.55 3.38 + 0.53 0.95 3.70 + 0.91 3.44 + 0.55 0.135

Ho ba teng ha fibrinogen e ntseng e eketseha 0.143 0.069 0.40 0.371 0.159 0.022

IL-6, pg / ml 5.94 + 3.89 5.70 + 1.31 0.94 2.43 + 0.51 4.41 + 1.08 0.10

Ts'ebetso ea Telomerase 0.51 + 0.09 0.60 + 0.05 0.36 0.47 + 0.08 0.62 + 0.07 0.063

Ts'ebetso ea "tlase" telomerase 0.512 0.417 0.56 0.710 0.474 0.049

Tafole ea 4. Matšoao a metabolism ea carbohydrate metabolism, khatello ea oxidative, ho ruruha ho sa foleng, bolelele ba telomere le telomerase (AT), ho latela boteng ba T2DM

Paramente SD2 + SD2- R

phahameng AT e tlase P P e phahameng AT tlase AT

HbA1c,% 7.19 + 0.60 7.36 + 0.80 0.45 5.19 + 0.58 5.35 + 0.41 0.16

GPN, mmol / L 7.55 + 1.40 8.47 + 1.79 0.09 5.17 + 0.51 5.33 + 0.44 0.14

MDA, μmol / L 2.93 + 0.90 3.23 + 1.01 0.34 3.06 + 0.93 3.34 + 0.72 0.25

IL-6, pg / ml 2.98 + 1.01 3.91 + 2.03 0.68 3.77 + 1.00 6.37 + 1.80 0.21

CRP, mg / L 5.34 + 1.40 7.12 + 1.76 0.43 4.14 + 0.78 2.55 + 0.26 0.06

Fibrinogen, g / l 3.62 + 0.70 3.66 + 0.85 0.87 3.60 + 0.50 3.37 + 0.43 0.034

Ho ba teng ha fibrinogen e ntseng e eketseha 0.375 0.259 0.43 0.205 0.075 0.09

Telomere e amanang le bolelele 9.77 + 0.50 9.43 + 0.42 0.02 9.81 + 0.51 9.70 + 0.45 0.33

bakuli ba phetseng hantle pakeng tsa batho ba nang le li-telomeres tse “khuts'oane” le tse telele, ho ne ho se na phapang e kholo mabapi le metabolism ea carbohydrate, ho teba ha khatello ea oxidative le ts'oaetso e sa foleng.

Ho bakuli ba T2DM le "telomeres" e khuts'oane, boemo ba CRP bo ne bo le holimo haholo 'me fiberrinogen e neng e eketsehile e ne e atile haholo. Phapang maemong a MDA, fibrinogen, IL-6 ha ea ka ea fumanoa. Ts'ebetso ea Telomerase e ne e le tlase hanyane ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 le li-telomeres tse khutšoanyane (9 = 0.063). Matšoao a "tlase" a ts'ebetso ea telomerase a ile a fumanoa ho bakuli ba nang le T2DM le "lifofane" mehato ea 'mele e khuts'oane hangata haholo (9 = 0.049).

Bathong ba nang le li-telomeres tse telele, matšoao a tšoaetso e sa foleng le khatello ea oxidative, hammoho le ts'ebetso ea telomerase, ba ne ba ikemetse ka mokhoa o ikemetseng boteng ba T2DM (Tafole ea 3).

Ts'ebetso ea Median telomerase e ne e le 0,50. Bakuli bohle ba nang le boleng bo tlase ba letšoao lena ba abeloa sehlopha sa "tlase" ts'ebetso ea telomerase, le bao mosebetsi oa bona oa telomerase o fetang boleng bona, ho sehlopha sa ts'ebetso e "phahameng" telomerase. Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, boemo ba metabolism ea carbohydrate, ts'ebetso ea matšoao a khatello ea nang le oxidative le ts'oaetso e sa foleng e ne e sa fapana lipakeng tsa lihlopha tsena, ntle le li-telomeres tse khuts'oanyane sehlopheng se nang le "tlase"

telomerase (p = 0.02). Sehlopha sa taolo le sona ha sea ka sa senola ho itšetleha ha maemo a khatello ea oxidative, CRP le IL-6 ts'ebetsong ea telomerase, leha ho le joalo, batho ba nang le "telomerase" e "phahameng" ba bonts'a maemo a holimo a fibrinogen (Tafole ea 4).

Ho bakuli ba T2DM le ts'ebetso ea "tlase" telomerase, CRP e ne e phahame, ho eketseha ha fibrinogen ho ne ho atile, 'me bolelele ba telomere bo ne bo le bokhutšoanyane. Maemo a IL-6, MDA le fibrinogen sehlopheng sa "telomerase" e tlase "e ne e sa itšetleha ka boteng ba T2DM. Ka sehlopha sa "high" telomerase shughuli, lifahleho tsa T2DM + le T2DM li ne li sa fapana ho latela khatello ea oxidative, ho ruruha ho sa foleng le bolelele ba telomere (Lethathamo 5).

Ho bakuli ba T2DM, mekhatlo e fumanoe pakeng tsa bolelele ba li-telomeres le GPN, CRP, ts'ebetso ea "telomerase" e tlase, empa ha ho tumellano e fumanoeng ka lilemo, khatello ea mali, BMI, HLA1c MDA, fibrinogen, le IL-6 (Lethathamo 6).

Sehlopha sa CD2 +, khokahano e nepahetseng e fumanoe feela pakeng tsa ts'ebetso ea telomerase le bolelele bo bolelele ba telomere. Sehlopheng sa taolo, ts'ebetso ea telomerase e ne e amana hantle le SBP, DBP, CRP le maemo a fibrinogen (Lethathamo 7).

Kamora moo, ho ile ha etsoa tlhahlobo e akaretsang ea ho khutlisetsa mela ka morao, moo bolelele ba li-telomeres bo sebelisitsoeng e le phetoho e fapaneng, mme lilemo, GPN, CRP, le "low" telomerase shughuli li ile tsa sebelisoa e le mefuta e ikemetseng. Ho ile ha fumaneha hore ke GPN le CRP feela tse ikemetseng tse amanang le bolelele ba telomere (Tafole ea 8).

Ha o sebelisa ts'ebetso ea telomerase e le phetoho e itšetlehileng ka eona, hape joalo ka ba ikemetseng - lilemo, DBP, GPN, CRP, fibrinogen, ho ile ha fumaneha hore sehlopheng sa CD2, ke DBP feela (karabo) le fiberrinogen (khokahano e tobileng) e amanang le boithatelo bo amanang le mosebetsi oa telomerase ( tafole ea 9). Ka sehlopha sa CD2 +, ho ne ho sena kamano e ikemetseng lipakeng tsa paramethara e ithutoang le tšebetso ea telomerase (Lethathamo 10).

Re fumane hore ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, bolelele ba mehato ea 'mele bo bokhutšoanyane ho feta ho batho ba phetseng hantle. Ho joalo

Lethathamo la 6. Tulo ea bolelele ba telomere le likarolo tse ling lihlopheng tse ithutileng (Likhakanyo tsa boemo ba puo)

SD2 + (n = 50) SD2- (n = 139) bolelele ba telomere bolelele

Lilemo, lilemo -0.09, p = 0.52 -0.18, p = 0.035

GARDEN, mmHg -0.036, p = 0.81 -0.14 p = 0.09

DBP, mmHg 0.066, p = 0.65 -0.03 p = 0.75

BMI, kg / m2 -0.025, p = 0.87 -0.13 p = 0.13

GPN, mmol / L -0.42, p = 0.0027 -0.16 p = 0.05

HbA1c,% -0.23, p = 0.12 -0.03 p = 0.69

MDA, μmol / L -0.17, p = 0.24 0.07, p = 0.55

CRP, mg / L -0.40, p = 0.004 -0.05 p = 0.57

Fibrinogen, g / l -0.18, p = 0.22 -0.04 p = 0.65

IL-6, pg / ml -0.034, p = 0.82 -0.04 p = 0.68

Ts'ebetso ea Telomerase 0.15, p = 0.33 0.03, p = 0.78

Ho ikoetlisa ka tlase

kopanya -0.32, p = 0.035 -0.06, p = 0.61

Tafole ea 7. Khokahano ea tšebetso ea telomerase le li-parameter tse ling lihlopheng tse ithutileng (Likhakanyo tsa boemo ba puo)

Ketsahalo ea telomerase SD2 + (n = 50) SD2- (n = 139)

Lilemo, lilemo tsa GARDEN, mm Hg DBP, mmHg BMI, kg / m2 GPN, mmol / L

Ho ba teng ha CRP Fibrinogen e eketsehileng, g / l IL-6, PG / ml

Bolelele bo lekanyang ba mehato ea 'mele

Mehato e melelele haholo ea 'mele

5, p = 0.35 2, p = 0.44 4, p = 0.37 -0.07, p = 0.65 -014, p = 0.38 -0.08, p = 0.64 - 0.064, p = 0.69 0.056, p = 0.73 0.03, p = 0.89-0.086, p = 0.59-0.006, p = 0.97

0.07, p = 0.52 0.20, p = 0.08 0.33, p = 0.003

-0,04 -0,17 -0,08 -0,11

p = 0.72 p = 0.14 p = 0.47 p = 0.47

0.11, p = 0.35 0.35, p = 0.002 0.28, p = 0.01 -0.19, p = 0.12

0.15, p = 0.33 0.03, p = 0.78 0.40, p = 0.0095 0.14, p = 0.22

e tsamaellanang le liphetho tsa bangoli ba bang. Leha ho le joalo, phuputsong e entsoeng ke M. Sampson et al. ha ho kamano e fumanoeng pakeng tsa ho khutsufatsoa ha bolelele ba li-lymphocytic telomeres le matšoao a metabolism ea carbohydrate (mohlomong ka lebaka la palo e nyane ea

Lethathamo la 5. Matšoao a khatello ea ts'oaetso ea oxidative, ho ruruha ho sa foleng le bolelele ba li-telomeres ho latela mosebetsi oa telomerase (AT)

Parameti Low AT High AT

SD2 + SD2- r SD2 + SD2- r

MDA, μmol / L 3.23 + 1.01 3.34 + 0.72 0.68 2.93 + 0.90 3.06 + 0.93 0.68

IL-6, pg / ml 3.91 + 2.03 6.37 + 1.80 0.37 2.98 + 1.01 3.77 + 1.00 0.62

CRP, mg / L 7.12 + 1.76 2.55 + 0.26 0.016 5.34 + 1.40 4.14 + 0.78 0.44

Fibrinogen, g / l 3.66 + 0.85 3.37 + 0.43 0.11 3.62 + 0.70 3.60 + 0.50 0.90

Ho ba teng ha fibrinogen e ntseng e eketseha 0,259 0.075 0.043 0.375 0.205 0.21

Telomere e amanang le bolelele 9.43 + 0.42 9.70 + 0.45 0.016 9.77 + 0.50 9.81 + 0.51 0.80

Tafole ea 8. Ho theoha ha bolelele ba telomere ka lilemo, GPN, CRP, ho fokotse ts'ebetso ea telomerase e le mefuta e ikemetseng ho bakuli ba nang le lefu la tsoekere la mofuta oa 2.

Paramente B E phoso e phoso P

Lilemo, lilemo -0.0008 -0.008 0.92

GPN, mmol / L -0.076 0.036 0,004

CRP, mg / L -0.018 0.007 0.020

Ketsahalo e “tlase” e monate

linako -0.201 0.125 0.116

Lethathamo la 9. Tekanyetso ea ts'ebetso ea telomerase ka lilemo, DBP, GPN, CRP, fibrinogen, GPN joalo ka mefuta e ikemetseng sehlopheng sa taolo

Paramente B E phoso e phoso P

Lilemo, lilemo -0.003 0.005 0.534

DBP, mmHg -0.010 0.004 0.012

GPN, mmol / L -0.105 0.081 0.20

CRP, mg / L 0.019 0.010 0.073

Fibrinogen, g / l 0.205 0.080 0.013

Lethathamo la 10. Ho theoha hoa ts'ebetso ea telomerase ka lilemo, DBP, GPN, CRP, fibrinogen, GPN joalo ka tse ling tse ikemetseng sehlopheng sa bakuli ba nang le lefu la tsoekere la mofuta oa 2.

Paramente B E phoso e phoso P

Lilemo, lilemo 0.002 0.008 0.74

DBP, mmHg -0.0001 0.006 0.98

GPN, mmol / L -0.006 0.039 0.15

CRP, mg / L 0.007 0.009 0.45

Fibrinogen, g / l -0.009 0.089 0.91

Sehlopha sa STI. Boithuto ba rona bo senotse phapang e kholo ho HbA1c le GPN ho bakuli ba T2DM ba nang le "telomeres" e telele le "e khuts'oane" hape ba fumane kamano e mpe lipakeng tsa bolelele ba telomere le GPN. Ho ka phetoa khang ea hore ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, li-telomeres tse khuts'oanyane li tsamaisana le taolo e mpe ea lefu la tsoekere, le hyperglycemia le eona e ka ba le tšusumetso e mpe ho botsofaling bo bongata.

Re fumane hore ts'ebetso ea telomerase ho bakuli ba nang le lefu la tsoekere la 2 e tlase ho feta ho batho ba phetseng hantle, e lumellanang le datha tse fokolang tse fumanehang. Karolo ea telomerase ts'ebetsong ea botsofali e tloaelehileng ea ithuta ebile ha e ithute ka mokhoa o sa lekanang. Ha rea ​​senola kamano pakeng tsa ts'ebetso ea telomerase le bolelele ba telomere, e lumellanang le maikutlo a hore karolo ea telomerase ha e na thuso ho boloka bolelele ba telomere homeostasis botsofaling.

Matla a senya a hyperglycemia ho biology ea telomeres, ho kenyeletsoa liseleng tsa endothelial, e lemohuoa ka mochine oa khatello ea oxidative le ts'oaetso e sa foleng. Leha ho le joalo, ea bohlokoa

Ho ne ho se na phapang boemong ba MDA lipakeng tsa lihlopha tsa T2DM + le T2DM (mohlomong ka lebaka la nako e khuts'oane ea lefu la tsoekere le ho se be le hyperglycemia e matla ea nako e telele, hobane hyperglycemia ea nako e telele e amana le nts'etsopele ea khatello e matla le e phehellang ea oxidative). Ho kanna ha hlokahala hore u sebelise matšoao a nepahetseng haholoanyane a khatello ea oxidative, joalo ka ho ntša moroto ha 8-iso-prostaglandin F2a. Re fumane matšoao a phahameng a tšoaetso ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 ho feta ho sehlopha se laolang. Letšoao le leng la ts'oaetso, IL-6, joalo ka ha e sa tsoa senoloa, e na le litlamorao tse ngata, e seng feela cytokine, empa le myokine, e tsosang myogenesis mme e ama hantle metabolism ea matla. Mohlomong ke ka lebaka leo boemo ba IL-6 taolong bo ileng ba hlaha bo batla bo le holimo, empa leha ho le joalo, bo hloka ho tsoela pele ho ithutoa.

Ho ruruha ho sa feleng ho lebisa ho botsofaling ba lisele pele ho nako, telomere e khutsufatsa ka ho kenya letsoho ho eketseha ha lisele tse nang le phepo le ho kenya letsoho tokollong ea ROS, ho baka ts'abo ea oxidative karolong ea lefu la DNA. Ka selemo sa 2012, ho ile ha bonts'oa hore khutsufatso e tsoelang pele ea li-telomeres ka keketseho ea nako ea T2DM e kanna ea amahanngoa le keketseho e ts'oanang ea khatello ea oxidative le ts'oaetso e sa foleng. Liphetho tsa rona li tsamaisana le datha tse tsoang lithutong tse fetileng. Re fumane maemo a phahameng a CRP le maemo a phahameng a MDA ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 le li-telomeres tse khutšoanyane ho feta ho bakuli ba nang le li-telomeres tse telele. Ho ne ho e-na le kamano e mpe lipakeng tsa bolelele ba lymphocyte telomere le letšoao la tšoaetso e sa foleng - CRP, e bonts'ang karolo ea ts'oaetso e sa foleng ea ho khutsufatsa ha telomere ho bakuli ba nang le lefu la tsoekere la mofuta oa 2. Sehlopheng sa taolo, ho ne ho sena khokahano lipakeng tsa CRP le bolelele ba telomere, bo lumellanang le liphetho tsa lithuto tse ling. Ho haella ha puisano pakeng tsa IL-6, fibrinogen, le bolelele ba telomere ka lihlopha tsena ka bobeli ho ka hlalosoa ka phapang e tlase ea matšoao ana. Ho feta moo, ho itšetleha feela ka boemo ba li-cytokine tse potolohang, motho a ka nyenyefatsa tekanyo ea ts'oaetso ea lehae liseleng.

Lintlha tsa lingoliloeng mabapi le kamano ea ts'oaetso e sa foleng le ts'ebetso ea telomerase lia hanyetsana. Ho ruruha ho sa feleng ha nako e telele ho lebisa ho fokotseheng ha telomerase, eo re e boneng ho bakuli ba nang le lefu la tsoekere la mofuta oa 2. Ka ts'oaetso e sa reroang le e sa sebetseng ea nako e telele, joalo ka lefu la metabolic kapa atherosulinosis, ho fapana le hoo, ho na le keketseho ea ketsahalo ea telomerase, eo mohlomong e leng tlatsetso tlholehong, e fokotsang ho fokotseha ha bolelele ba telomere liseleng tse arohaneng

tlasa ts'usumetso ea li-cytokines tse fokotsang. Ka 'nete, sehlopheng sa taolo, re fumane kamano e ntle lipakeng tsa ts'ebetso ea telomerase le matšoao a tšoaetso e sa foleng.

Ho bohlokoa ho totobatsa hore, ho ea ka data ea rona, boemo ba khatello ea oxidative, ho ruruha ho sa foleng le ts'ebetso ea telomerase ho bakuli ba nang le T2DM le li-telomeres tse "telele" li ne li sa fapana haholo le li-indices tse tsamaeang le batho ba phetseng hantle. Ho ka nahanoa hore ka nako e khuts'oane ea T2DM, bolelele ba bolelele bo bolelele ba telomere bo sireletsa bakuli liphellong tse mpe tsa khatello ea oxidative le ts'oaetso e sa foleng, ho fana ka tsosoloso e ntle le e potlakileng ea lisele tse senyehileng, ho kenyeletsoa le methapo ea mali. Ho fapana le hoo, ho bakuli ba T2DM le li-telomeres tse “khutšoanyane”, esita le nako e khuts'oane ea lefu lena, ho teba ha tšoaetso e sa foleng le tekanyo ea ho fokotseha hoa ts'ebetso ea telomerase e ne e le bohlokoa le ho feta. Re lokela ho hopola hore bakuli ba lefu la tsoekere la mofuta oa 2 le taolo ba ne ba ka bapisoa ka lilemo.

Ho na le bopaki bo ntseng bo hola ba hore telomere e khutsufatsa ke karolo ea bohlokoa ho fokotseng litsi tsa polokelo ea lisele le ho senyeha ha lisele tse amanang le botsofaling. Kopano ea T2DM le ts'ebetso ea botsofaling ba lisele le ho teba ha ts'oaetso e sa feleng le khatello ea maikutlo li ka hlalosa sesosa se phahameng sa CVD ho lefu lena. Boithuto bo eketsehileng bo tla lumella ho nka hloko bolelele ba telomere har'a bakuli ba nang le lefu la tsoekere la mofuta oa 2, sehlopha sa batho ba hlokang taolo e matla ea metabolism ea carbohydrate, e tla fana ka mokhoa o ikhethileng haholoanyane oa kalafo ea lefu lena.

1. Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, bolelele ba telomere bo bokhutšoanyane, 'me mosebetsi oa telomerase o tlase ho feta ho batho ba phetseng hantle. Boleng ba ts'ebetso ea boitlamo ba 'mele ho fetola bolelele ba li-telomeres ha boa ka ba pepesoa.

Boemo ba MDA ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 le batho ba phetseng hantle bo batla bo batla bo tšoana. Ho ruruha ho sa feleng ho boleloa haholo ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 ho feta ho batho ba phetseng hantle ba lilemo tse tšoanang. Ho ruruha ho sa feleng ho bapala karolo e ka sehloohong ho khutsufatsang li-telomeres le tšebetso e eketsehang ea telomerase.

3. Ho bakuli ba nang le T2DM le li-telomeres tse “telele”, ho teba ha khatello ea oxidative le ho ruruha ho sa foleng ha ho fapana le litekanyetso tse tsamaellanang ho batho ba phetseng hantle.

4. Ho bakuli ba nang le T2DM, li-telomeres tse “khutšoane” li amahanngoa le taolo e mpe ea lefu la tsoekere le ho ruruha ho matla ho sa foleng.

5. Li-telomere tse "telele" li sireletsa bakuli ba nang le lefu la tsoekere liphellong tse mpe tsa khatello ea maikutlo le ho holofala ho sa feleng.

Ha ho na likhohlano tsa phaello.

Boithuto bona bo ile ba etsoa e le karolo ea mosebetsi oa Naha "Boithuto ba methapo ea limolek'hule ea atherogeneis e le ho nts'etsapele mekhoa ea tlhahlobo ea kalafo ea lefu la kalafo ea methapo e le mokhoa o ka sehloohong oa ho thusa mafu a pelo le mathata a ona."

Mohopolo oa lipatlisiso le moralo - E.N. Dudinskaya, O.N. Tkacheva, I.D. Strazhesko, E.V. Akasheva.

Ho bokella le ho lokisa thepa - N.V. Brailova, E.V. Plohova, V.S. Pihtina.

Ts'ebetso ea data ea Statistical - V.A. E na le thuso.

Ho ngola sengoloa - N.V. Brailova.

Editing - E.N. Dudinskaya, O.N. Tkacheva, M.V. Shestakova, S.A. Lintoa.

Sehlopha sa bangoli se leboha A.S. Kruglikov, I.N. Ozerov, N.V. Gomyranova (Setheo sa Budgetary Budgetary Institution "Setsi sa Patlo ea Naha sa Phekolo ea Thibelo ea Ts'ireletso" sa Lekala la Bophelo la Russian Federation) le D.A. Skvortsov (Setsi sa Biology ea K'hemik'hale ea 'mele le K'hemik'hale e reheletsoeng ka AN ANZzzkykyOUOU VPO e reheletsoeng ka MV Lomonosov) bakeng sa thuso ea ho etsa thuto.

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