中文摘要：

目的探讨氧化应激诱导心肌细胞凋亡是否与内质网应激（endoplasmic reticulum stress,ERS）的调控机制有关。方法给予乳鼠心肌细胞高低两种浓度（500、100μmol/L）和不同时间（0、4、8、12、24h）过氧化氢（H2O2）刺激。采用流式细胞仪检测各组心肌细胞的凋亡率;苏木精-伊红染色法（HE）观察心肌细胞凋亡的典型形态;通过Western blot检测ERS标志蛋白p-PERK和CHOP的表达变化。进一步采用ERS抑制剂化学伴侣PBA（4-phenylbutyric acid）抑制心肌细胞ERS,Western blot检测p-JNK、p-PERK和CHOP蛋白的表达变化;采用流式细胞仪检测Caspase-12和Caspase-3的活性。结果①低浓度H2O2可显著诱导心肌细胞凋亡,高浓度H2O2则导致心肌细胞发生坏死;100μmol/L H2O2刺激心肌细胞8h时其凋亡率最高。②心肌细胞发生凋亡时ERS标志蛋白p-PERK和CHOP表达显著增高。③ERS抑制剂PBA预处理心肌细胞,可有效抑制H2O2诱导的p-PERK、CHOP表达及Caspase-3、Caspase-12活性的上调,与单纯H2O2处理组相比差异有统计学意义（P〈0.01）。结论低浓度H2O2可通过促发ERS整合调控机制介导心肌细胞凋亡。这一结果将从ERS整合调控细胞应激的角度为心血管疾病的防治提供新思路。

英文摘要：

Objective To investigate relationship between the apoptosis of cardiomyocyte induced by oxidative stress and the endoplasmic reticulum stress（ERS）.Methods The cultured H9C2 cells were divided into 2 groups：low concentration（100 μmol/L H2O2）group and high concentration（500 μmol/L H2O2）group at different time points.The apoptosis rate was detected by flow cytometry and the typical cardiomyocyte apoptosis was observed by hematoxylin-eosin（HE）staining.The expression of ERS marker proteins p-PERK and CHOP was detected by using Western blot.The chemical chaperone 4-phenylbutyric acid（PBA）was used to inhibit ERS in myocardial cells and the expression of p-JNK,p-PERK and CHOP was detected by using Western blot.The activities of Caspase-12 and Caspase-3 were measured by using flow cytometry.Results ① The highest rate of apoptosis was observed in the myocardial cells treated with H2O2（100 μmol/L）for 8 h.② The expression of ERS marker proteins p-PERK and CHOP was significantly higher in the H2O2 groups.③PBA could effectively inhibit H2O2-induced apoptosis of cardiomyocytes,significantly down-regulate the expression of ERS marker proteins p-PERK and CHOP（P0.01）,and significantly reduce the activities of Caspase-3 and Caspase-12（P0.01）.Conclusion The low concentration of H2O2（100 μmol/L）significantly induced the apoptosis of myocardial cells via triggering ERS regulation mechanism and high concentration of H2O2（500 μmol/L）resulted in myocardial necrosis.Our results could provide new clues for prevention and treatment of cardiovascular diseases.