右美托咪定对乳大鼠心肌细胞线粒体活性氧和细胞凋亡的影响

Effects of dexmedetomidine on ROS and apoptosis in neonatal rat cardiac muscle cells

目的:探讨右美托咪定(Dexmedetomidine,DEX)对线粒体介导的乳大鼠心肌细胞氧化应激通路的作用。方法:取新生乳大鼠(3~4天)的心肌进行原代培养,培养24h后分为对照组(C组)、H_2O_2组(终浓度500μM,H组)、右美托咪定组(5μM DEX,D组)、联合用药组(500μM H_2O_2+5μM DEX,DH组)。各组细胞分别给予相应药物刺激6h,采用流式细胞仪测定活性氧自由基(Reactive oxygen species,ROS)水平及心肌细胞凋亡变化;并通过ELISA法测定各组乳大鼠心肌细胞线粒体介导的凋亡因子Caspase-3,Caspase-9表达的变化。结果:与H_2O_2组相比,DEX明显抑制H_2O_2介导的乳大鼠心肌细胞的ROS水平增加(P<0.05);下调线粒体介导的下游凋亡因子Caspase-3,Caspase-9的表达(P<0.05),从而减少H_2O_2诱导的凋亡(P<0.05)。结论:右美托咪定通过抑制心肌细胞活性氧水平以及下调线粒体介导的Caspase-3和Caspase-9的表达发挥抑制凋亡作用,对心肌细胞有一定的保护作用。

Objective：To investigate the effects of dexmedetomidine（DEX）on ROS and apoptosis in neonatal rat cardiac muscle cells.Methods：Neonatal rats（3-4days）cardiomyocytes（NRCMs）were cultured for 24 hand divided into four groups：control group（Group C）,H2O2group（final concentration of 500μM,Group H）,dexmedetomidine group（5μM DEX,group D）,and H2O2＋DEX group（500μM H2O2＋ 5μM DEX,group DH）.Flow cytometry（FCM）was used to measure the effect of DEX on the ROS level and apoptosis of myocardial cells in rats.The level of Caspase-3and Caspase-9were detected by ELISA.Results：DEX significantly inhibited the increase of ROS levels in NRCMs induced by H2O2（P〈0.05）.The increased level of Caspase-3,Caspase-9induced by H2O2 was significantly inhibited by DEX（P〈0.01 or P〈0.05）.DEX significantly attenuated cells ratio of apoptosis induced by H2O2（P〈0.05）.Conclusion：Dexmedetomidine inhibited the ROS levels and the activity of mitochondria mediated Caspase-3and Caspase-9expression and attenuated H2O2-induced apoptosis in myocardial cells,which may involved in the myocardial protective effect of DEX.