曲美他嗪对缺氧诱导原代大鼠心肌细胞凋亡的影响  

The influence of trimetazidine on the apoptosis induced by hypoxia in the rat cardiac myocytes

作　　者：付尧[1] 汉雯 白小涓[1] FU Yao HAN Wen BAI Xiao-Juan(Department of Gerontology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110001, China)

机构地区：[1]中国医科大学附属盛京医院老年病科,辽宁省沈阳市110001

出　　处：《中国动脉硬化杂志》2017年第10期1002-1007,共6页Chinese Journal of Arteriosclerosis

摘　　要：目的研究曲美他嗪对缺氧诱导的心肌细胞凋亡及线粒体能量代谢改变的影响。方法采用胰酶和胶原酶联合消化的方法,提取大鼠原代心肌细胞,三气培养箱模拟缺氧损伤。MTT和Hoechst染色检测细胞活性和凋亡,TMRE染色检测线粒体膜电位,Oxygraph-2k细胞呼吸测量仪检测态3、态4呼吸和呼吸控制率,Western blot检测Caspase-3、细胞色素C以及线粒体呼吸链复合酶体Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ蛋白表达水平的变化。结果缺氧能够诱导心肌细胞凋亡、引起线粒体膜电位下降和促进细胞色素C的释放。此外,缺氧能够显著下调态3呼吸和上调态4呼吸,引起呼吸控制率的下降,同时缺氧能够不同程度地下调线粒体呼吸链复合酶体Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ的蛋白表达水平。曲美他嗪能够显著降低缺氧诱导的心肌细胞凋亡、稳定线粒体膜电位和减少细胞色素C释放。此外,曲美他嗪还能减轻缺氧对线粒体呼吸链复合酶体的损伤,维持线粒体有氧呼吸。结论曲美他嗪具有抵抗缺氧致心肌细胞凋亡的作用,可能与其稳定线粒体膜和呼吸链复合酶体有关,继而减少细胞色素C的释放和维持线粒体有氧呼吸。Aim To study the protective effect of trimetazidine （TMZ） on hypoxia jury in the rat cardiac myo- cytes. Methods Primary myocardial ceils of rat were cultured in incubator at 37℃ with 94% N2 ＋5% CO2 ＋ 1% O2. Cell viability was detected by MTY. Apoptosis was detected by Hoechst staining. Mitochondrial membrane potential （MMP） was detected by TMRE. Mitochondrial energy metabolism was detected by Oxygraph-2k. Caspase-3, cytochrome C and respiratory chain complex enzymes were detected by Western blot. Results Hypoxia could induce apoptosis in the rat cardiac myocytes, decrease of MMP, cytochrome C release to cytosol. Furthermore, hypoxia could de- crease state 3 respiration and respiratory control rate, increase state 4 respiration and decrease the expression of respiratory chain complex enzymes. Meanwhile, TMZ could play a protective effect against the apoptosis induced by hypoxia in the rat cardiac myocytes. It may be related to its protective role on MMP and respiratory chain complex enzymes. Conclusion TMZ could inhibit the apoptosis of rat cardiac myocytes induced by hypoxia via the mitochondrial pathway.

关 键 词：缺氧 曲美他嗪 心肌细胞 细胞凋亡 线粒体能量代谢 

分 类 号：R541.4[医药卫生—心血管疾病]