JNK抑制剂对H_2O_2诱导心肌细胞凋亡的保护作用

Role of JNK inhibitor in protection of cardiomyocytes apoptosis induced by H_2O_2

目的观察特异性JNK抑制剂对H2O2诱导凋亡的培养乳鼠心肌细胞的保护作用,探讨热休克蛋白70(HSP70)对H2O2诱导心肌细胞凋亡的保护作用机制。方法培养大鼠乳鼠心肌细胞,随机分为4组,即正常对照组、H2O2损伤组、热休克组和JNK抑制剂组。应用免疫组化技术检测HSP70的表达;用透射电镜观察心肌细胞超微结构变化;用流式细胞仪分析心肌细胞凋亡百分率。结果热休克预处理后HSP70在细胞浆内大量表达。JNK抑制剂明显抑制心肌细胞的凋亡率。结论热应激预适应和JNK抑制剂对心肌细胞都具有保护作用,其保护机制可能与热应激时HSP70在心肌细胞内大量表达从而抑制了JNK的信号转导有关。

Objective To discuss the relationship between heat shock protein 70 （HSP70） and neonatal rat cardiomyocytes apoptosis induced by H2O2 through observing the protection of JNK inhibitor on the isolated neonatal rat cardiomyocytes injured by H2O2. Methods Cardiomyocytes were cuhured in vitro and divided into four groups： control group, injured group by H2O2, heat shock group and JNK inhibitor group. The up-regulation of HSP70 was tested by immunohistochemical method. Apoptosis of cardiomyocytes was determined by flow cytometry （FCM） and transmission electmnmicmscope （TEM）. Results The up-regulation of HSP70 was demonstrated by i mmunohistochemistry. The apoptosis rate was siguificantly lower in the heat shock group and JNK inhibitor group than in the injured group. Conclusion Both HSP70 and JNK inhibitor can delay apoptosis induced by H2O2 and protect myocardial cell. The possible mechanisms are as follows： Heat shocking make HSP70 up-regulated, the latter can meditate suppression JNK, an early component of stress-induced apoptotic signaling pathway. These observations can provide a basis for the function of HSP70 in anti-apoptosis.