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???????λ?????? > ?????? > ????????? >
??????????HIF-?????о????????
???????2019-10-08

???????? ???????????????-α (HIF-α) ???????????е??????????, ??????????????????????, ??????????????????????????á?HIF-α??????????м????????, ???????????±?????????????, ???????????????????????????????????????????????á?

??????????????????????-α; ????; ???????????; ????;

?????????????? (hypoxia inducible factor, HIF) ?????α?????β??????????????, ????HIF-α????λ??14???????q21-24??, ????????????????????HIF-α?????????????????μ???????????[1], ??????????????о?, ??????????????????????о???????????HIF-α????????????????о???????????

????1?? HIF-α??????

????????????????????缏Χ????????????????, ????????й???????й???????????????????200%?????HIF-α????????????????, ????Duennwald????2013???о???Ъ???????????????????????????Duennwald???????????????HIF-α?????????????, ?????????????????????????????????[2]????????????о???????HIF-α?????????????????????????о????????????????????????HIF-α??????????????????, ???????????????????????????????????????С??HIF-α?????ó???鷢??HIF-α?????????????????????з????????????????[3]?????HIF-α???????????????????????????????????????о?????CoCl2????????????????HIF?????, ?????????HIF?л????????????????????CoCl2????????????????????, ???????HIF-α?????й????????????????????????????????, ???????????[4]???????????????????????????????????????????????о???÷????????о??????????????????????????????????α??????????????????????????????????????????????????HIF-α?????????, ??????????????HIF-α???????????????, ?????????????????, ?????????????????????????????????[5]????????????????????????HIF-α????????, ???????????, ?????????????????????????????HIF-α???????????????????????, ???????????????Ч???????????????????????????????????????????????????HIF-α???????????????????????????y?????о???

????2 ??HIF-α?????????????

????2.1?? HIF-α????????????????

?????????о?????, ???????????????????????HIF-α?????????????????????á??о???????HIF-α????????????????·?????, ??????????????????????????????????Щ????????·??????????????????κB?????HIF-α??γ-?????????????????????????????????????????Ρ????о?[6]????γ-??????????HIF-α????????е???????, ?????HIF-α?????????, ??????????????????????????????????????????κB?·??HIF-α??????γ-??????????????????????TER?????????, ?????????????????????????????????HIF-α?????????????????????????, ?????????????????????????????????, HIF-α?????????????????????á?
?

??????????HIF-?????о????????
?

????2.2?? HIF-α??????????????

?????????????HIF-α????????????, HIF-α??????????????????????????????? (vascular endothelial growth factor, VEGF) ???????????????????????[7], ???????????????з????????á???????????????????????, ??????????????????????????, ?????????, ??????????????????????????????[8,9]????HIF-α???????????з???????????????????????о?????[10], ??????????HIF-α???????????-?????????????????;???????????, HIF-α????????????, ????HIF-α?????????????, ????HIF-α?????????????????????, HIF-α?????VEGF????, ????????????????????????????????????, ??????????HIF-α??????????????????????????????????, ??????????????????????????á?

????2.3?? HIF-α?????????????

????Hotamisligil????1993????, ?????????????????????????????????????????????????????[11]??HIF-α??????????????е???????????????? (inducible nitric oxide synthase, iNOS) ????, iNOS??????????L-??????????????????, ??????NO???????????????????????????????о?[12]????????????????????????????HIF-α??mRNA????, ???HIF-α?????????????????????????HIF-α???????????, ??????????????, ??????????в????, ???????????????????л????????????????????????巢???????????????????????о???

????3?? HIF-α??????

????HIF-α????????????????ε????ал?????EPO??VEGF??GLUT?????, ????????????л??????????????????????[13]??

????3.1?? HIF-α???С???????е?????

????????????????????????????????λ, ????С?????? (non-small cell lung cancer, NSCLC) ?????о?????λ, ??????80%[14]???????[15]?о???????HIF-α??VEGF??NSCLC????????????????, ???????????NSCLC??????Э????á??????????[13]???о????????, ??NSCLC??HIF-α???????VEGF??????????????????γ?, ???????????????????????????????????????????????????VEGF????????????????, HIF-α????VEGF??з??μ??????????????????????????, ?????з???????????????

????3.2?? HIF-α??????????е?????

???????????????????????, ????????????????????????????????, ?????????????????????????????????????????????????о?????, HIF-α????????????????????????γ????????????????1????[16]?о?????HIF-α???????????г??????, ??HIF-α?????????????????????????????????, ??y??????????????, ??????????????????????[17], ??????????????????????????????????????HIF-α????????????????????????????????????????????????о????????

????3.3?? HIF-α????????е?????

????????????????????????, ?????Χ????????????????, ?????????????, ????????????????[18]???????[19]????HIF-α???????????г????????????????????????й?, HIF-α?????????????????????, ?????????????, ???е????????е??????????ɡ????迵??[20]??????????????????HIF-α????????????, ???????????????????????????????????????????б???, ????????д?????????о???

????????????, HIF-α??????????????????????????????NSCLC?????????????????????????е???Щ???????????????????????????????, ?????о???????????????????о?????????????????з?????????塣????HIF-α????Щ????????????в????, ???????????н???????о???

?????ο?????

????[1] SHARP F R, BERNAUDIN M.HIF1 and oxygen sensing in the brain[J].Nat Rev Neurosci, 2004, 5 (6) :437-448.
????[2] DUENNWALD T, GATTERER H, GROOP P H, et al.Effects of a single bout of interval hypoxia on cardiorespiratory control and blood glucose in patients with type 2 diabetes[J].Diabetes, 2013, 62 (12) :4220-4227.
????[3] ????.????????ó??????????HIF-1α???????????????[D].????:??????, 2014.
????[4] ??????, ????, ???, ??.??????????????????????????HIF-1α???P????[J].????????????, 2014, 28 (11) :1061-1063.
????[5] ÷????.HIF-1α?????????????????????????е?????????о?[D].???:?????????, 2017.
????[6] ????Ρ.NF-κB/HIF-1α?·??IFN-γ????????????????е?????о?[D].???:??????????, 2014.
????[7] ????, ????, ????, ??.??????????????????????????????HIF-1??VEGF????[J].??????????? (????????) , 2012, 32 (8) :1047-1051.
????[8] QIN F, LIU Y X, ZHAO H W, et al.Chinese medicinal formula Guan-Xin-Er-Hao protects the heart against oxidative stress induced by acute ischemic myocardial injury in rats[J].Phytomedicine, 2009, 16 (2/3) :215-221.
????[9] ZALEWSKI J, NESSLER J.The endogenous cardioprotection during reperfusion in acute myocardial infarction[J].Kardiol Pol, 2011, 69 (Suppl.3) :67-74.
????[10] ???, ?????, ?????, ??.???з?????????????????????????????????????HIF-α??VEGF???????[J].????????? (????) , 2013, 39 (6) :1159-1163.
????[11] HOTAMISLIGIL G S, SHARGILL N S, SPIEGELMAN B M.Adipose expression of tumor necrosis factor-alpha:direct role in obesity-linked insulin resistance[J].Science, 1993, 259 (5091) :87-91.
????[12] ?????, ??????.?????????AdipoRon???????С????????????????[J].?????????????, 2015, 32 (4) :468-475.
????[13] ??????, ??????, ???′?.NADPH???????HIF-α???????е???????[J].????????, 2016, 36 (5) :691-697.
????[14] SUBRAMANIAN J, MORGENSZTERN D, GOODGAME B, et al.Distinctive characteristics of non-small cell lung cancer (NSCLC) in the young:a surveillance, epidemiology, and end results (SEER) analysis[J].J Thorac Oncol, 2010, 5 (1) :23-28.
????[15] ???, ???, ??????, ??.HIF-α??VEGF??DLL4???С???????е??P???????[J].?????????, 2016, 28 (5) :44-47.
????[16] ?1???, ????.HIF-α???????????е?????????????[J].???????????, 2016, 29 (20) :3535-3537.
????[17] PAULIS Y W, SOETEKOUW P M, VERHEUL H M, et al.Signalling pathways in vasculogenic mimicry[J].Biochim Biophys Acta, 2010, 1806 (1) :18-28.
????[18] ????, ?????, Τ???, ??.??????????????????????????????????????[J].????????????, 2014, 31 (3) :438-439.
????[19] ????, ???.AKT2??HIF-1α????????е??P??????[J].?й??????, 2012, 10 (12) :428-430.
????[20] ???迵, ????, ????, ??.?????????????????????????????-1α???????????????[J].?????????о?, 2015, 42 (10) :993-996.

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