缺氧诱导因子-1α对脂多糖所致心肌细胞线粒体功能损伤的影响  

Effects of HIF - la on mitochondrial function of cardiomyocytes stimulated by lipopolysaccharide

作　　者：杨乐[1] 邹晓静[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院急诊内科,武汉430030 [2]华中科技大学同济医学院附属协和医院麻醉科

出　　处：《中华急诊医学杂志》2012年第8期836-839,共4页Chinese Journal of Emergency Medicine

基　　金：国家自然科学基金（30901405、81102691）

摘　　要：目的探讨心肌细胞缺氧诱导因子-1α（hypoxia—induciblefactor-1α，HIF-1α）对脂多糖（1ipopolysaccharide，LPS）诱导心肌细胞线粒体功能损伤的影响。方法培养新生乳鼠心肌细胞，随机（随机数字法）分为4组。①C组：常规心肌细胞培养，不予任何处理；②LPS组：给予1bLg／mILPS，培养2h；③YC．1＋LPS组：预给HIF-1α特异性抑制剂YC-l 4μmol／L培养8h，再加入1恤∥mlLPS，培养2h；④YC-1组：仅给予4mol／LYC—l培养8h。利用荧光分光光度计测定线粒体膜电位（mitoehondrialmembranepotential，MMP），荧光素酶法测定细胞ATP含量，比色法测定细胞色素C氧化酶（cytochromeCoxidase，COX）活性，Westernblot测定细胞色素氧化酶亚单位1，2的蛋白表达水平。结果与c组相比，LPS显著抑制心肌细胞MMP、COX活性，AT／）含量也显著降低（P〈0．05），并抑制COX-1蛋白表达（P〈0．05），上调COX-2蛋白表达（P〈0．05）。与LPS组相比，HIF-1理抑制剂YC-1能进-步降低心肌细胞MMP、COX活性及ATP含量（P〈0．01），显著增加COX-1表达并使COX-2表达的下调（P〈0．01）。结论HIF．1cc抑制剂YC．1可能通过改变COX-1及COX-2表达，加重LPS所致的心肌细胞线粒体功能的损伤，提示HIF-α对LPS诱导的心肌细胞线粒体损伤可能具有保护作用。Objective To investigate the effects of HIF-la, on mitochondrial function of cardiomyoeytes stimulated by lipopolysaccharide （LPS）. Methods Cultured neonatal cardiomyocytes were randomly （ random number） distributed to four groups （ n = 5 ）. Control group： the neonatal cardiomyocytes were cultured in normal condition without any treatmeat; LPS group： cardiomyocytes were exposed to 1 p.g/ml LPS for 2 h; YC-1 ＋ LPS group： cardiomyocytes were exposed to 4 p, mol/L YC-1 for 8 h before LPS treatment; YC-1 group： cardiomyocytes were exposed to 4 mol/L YC-1 for 8 h. As indexes of mitochondrial function, MMP, the content of ATP and the activity of cytochrome oxidase were measured, COX1/2 protein expression was determined by Western blotting. Results Compared with control group, LPS decreased MMP, the content of ATP and the activity of COX obviously （P 〈 0. 05）, depressed the expression of COX- 1 protein （ P 〈 0.05 ）, induced the expression of COX-2 protein （ P 〈 0.05 ）. Compared with the LPS group, MMP, the content of ATP and the activity of COX were markedly attenuated （P 〈 0. 01 ）, the expression of COX-1 was significantly increased and the expression of COX-2 was decreased in theYC-1 ＋ LPS group （P 〈 0.01 ）. Conclusions YC-1 attributes to the dysfunction of mitoehondrial of myocyte by alterating the expression of COX-1 and 2, HIF-1α may attenuate the mitoehondrial dysfunction of cadiomyocytes stimulated by LPS.

关 键 词：脂多糖 缺氧诱导因子-1Α 心肌细胞 线粒体 

分 类 号：R285.5[医药卫生—中药学]