低氧环境对高原鼠兔骨骼肌HIF-1α和VEGF表达的影响
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摘要
研究了在低氧应激条件下,世居高原小哺乳动物高原鼠兔(Ochotona curzoniae)和SD大鼠(Rattus norregicus)骨骼肌中HIF-1α和VEGF的蛋白质水平变化及HIF-1α和VEGF的相关性。运用双位点免疫酶测定法(ELISA)检测骨骼肌中HIF-1α和VEGF的表达水平。结果表明,在低氧暴露(6 h)条件下,高原鼠兔和SD大鼠氧化和糖酵解型肌纤维中HIF-1α和VEGF的表达水平都显著高于常氧组(P<0.05)。同时发现,HIF-1α和VEGF在高原鼠兔骨骼肌中的表达增高量要显著低于SD大鼠(P<0.05)。此外,在低氧胁迫条件下,SD大鼠(n=20)和高原鼠兔(n=15)骨骼肌的氧化型肌纤维中HIF-1α和VEGF的增高(r=0.76,P<0.01)和糖酵解型肌纤维中HIF-1α和VEGF的增高(r=0.72,P<0.01)存在线性关系。同时抑制HIF-1α的表达能够显著降低骨骼肌中VEGF的表达(P<0.05)。结论 :(1)在低氧应激条件下,对比SD大鼠,高原鼠兔骨骼肌中HIF-1α和VEGF的反应功能表现出不敏感型;(2)在低氧环境中,HIF-1α对骨骼肌中VEGF起调节作用。
We investigated the levels of hypoxia-inducible factor 1-alpha( HIF-1 α) and vascular endothelial growth factor( VEGF) in skeletal muscles of plateau pika( Ochotona curzoniae), a small native plateau ochotonid lagomorph, in response to hypoxia. We compared these data with those for SD rats( Rattus norvegicus). We analyzed the relationship between HIF-1 α and VEGF in skeletal muscle of plateau pika. Levels of HIF-1 α and VEGF were estimated by use of ELISA methods.Results demonstrated that hypoxic stress induced by exposure to reduced levels of O2 for 6 h significantly increased the levels of HIF-1 α and VEGF in the oxidative and glycolytic muscles of SD rats and pikas( P < 0. 05 vs. normoxic conditions). Notably, the increases in levels of HIF-1 α and VEGF were significantly less pronounced in pikas( P < 0. 05, vs. SD controls) than in SD rats.We documented a linear relationship between amplified HIF-1 α and VEGF in oxidative muscle( r =0. 76 and P < 0. 01) and glycolytic muscle( r = 0. 72 and P < 0. 01). Inhibition of HIF-1 α significantly reduced expression of VEGF( P < 0. 05). Overall, our findings suggest that:( 1) responsiveness of HIF-1 α and VEGF in skeletal muscles to hypoxic stress is blunted in plateau animals; and( 2)HIF-1 α has a regulatory effect on VEGF under hypoxic environment.
We investigated the levels of hypoxia-inducible factor 1-alpha( HIF-1 α) and vascular endothelial growth factor( VEGF) in skeletal muscles of plateau pika( Ochotona curzoniae), a small native plateau ochotonid lagomorph, in response to hypoxia. We compared these data with those for SD rats( Rattus norvegicus). We analyzed the relationship between HIF-1 α and VEGF in skeletal muscle of plateau pika. Levels of HIF-1 α and VEGF were estimated by use of ELISA methods.Results demonstrated that hypoxic stress induced by exposure to reduced levels of O2 for 6 h significantly increased the levels of HIF-1 α and VEGF in the oxidative and glycolytic muscles of SD rats and pikas( P < 0. 05 vs. normoxic conditions). Notably, the increases in levels of HIF-1 α and VEGF were significantly less pronounced in pikas( P < 0. 05, vs. SD controls) than in SD rats.We documented a linear relationship between amplified HIF-1 α and VEGF in oxidative muscle( r =0. 76 and P < 0. 01) and glycolytic muscle( r = 0. 72 and P < 0. 01). Inhibition of HIF-1 α significantly reduced expression of VEGF( P < 0. 05). Overall, our findings suggest that:( 1) responsiveness of HIF-1 α and VEGF in skeletal muscles to hypoxic stress is blunted in plateau animals; and( 2)HIF-1 α has a regulatory effect on VEGF under hypoxic environment.
引文
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[2]Manalo D J,Rowan A,Lavoie T,et al.Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1[J].Blood,2005,105(2):659-669.
[3]Ratcliffe P J.HIF-1 and HIF-2:working alone or together in hypoxia[J].The Journal of Clinical Investigation,2007,117(4):862-865.
[4]Wubs M,Saito K,Kohler S,et al.Gauging a quantum heat bath with dissipative Landau-Zener transitions[J].Physical Review Letters,2006,97(20):200404.
[5]Kim Y W,Byzova T V.Oxidative stress in angiogenesis and vascular disease[J].Blood,2014,123(5):625-631.
[6]杜继曾,李庆芬.模拟高原低氧对高原鼠兔和大鼠器官与血液若干指标的影响[J].兽类学报,1982,2(1):35-42.
[7]Grace C R,Perrin M H,Di Gruccio M R,et al.NMR structure and peptide hormone binding site of the first extracellular domain of a type B1 G protein-coupled receptor[J].Proceedings of the National A-cademy of Sciences of the United States of America,2004,101(35):12836-12841.
[8]Zbytek B,Slominski A T.Corticotropin-releasing hormone induces keratinocyte differentiation in the adult human epidermis[J].Journal of Cellular Physiology,2005,203(1):118-126.
[9]谢惠春,罗巧玉,陈志,等.高原鼠兔繁殖季节血液指标、血气及性激素变化[J].野生动物学报,2017,38(2):205-214.
[10]Lieber R L.Skeletal muscle structure,function,and plasticity[M].Maryland,USA:Lippincott Williams&Wilkins,2009:116-200.
[11]Chen Xuequn,Wang Shijun,Du Jizeng,et al.Diversities in hepatic HIF-1,IGF-I/IGFBP-1,LDH/ICD,and their mRNA expressions induced by Co Cl2in Qinghai-Tibetan plateau mammals and sea level mice[J].American Journal of Physiology-Regulatory Integrative and Comparative Physiology,2007,292(1):R516-R526.
[12]Pisani D F,Dechesne C A.Skeletal muscle HIF-1alpha expression is dependent on muscle fiber type[J].The Journal of General Physiology,2005,126(2):173-178.
[13]Lin Jiandie,Wu Hai,Tarr P T,et al.Transcriptional co-activator PGC-1αdrives the formation of slow-twitch muscle fibres[J].Nature,2002,418(6899):797-801.
[14]Grange R W,Meeson A,Chin E,et al.Functional and molecular adaptations in skeletal muscle of myoglobin-mutant mice[J].A-merican Journal of Physiology-Cell Physiology,2001,281(5):C1487-C1494.