四逆汤抗阿霉素性心衰心肌细胞线粒体凋亡机制探讨

Effects of Sini decoction on mitochondrial mediated apoptosis in adriamycin-induced heart failure rats

目的探讨四逆汤抗阿霉素(ADR)性心衰大鼠心肌细胞凋亡的作用及线粒体机制。方法 SD大鼠随机分为对照组,心衰组和四逆汤组,心衰组和四逆汤组尾静脉注射ADR复制心衰模型,四逆汤组给予四逆汤煎剂灌胃(3.75g生药/kg/d),实验结束时留取各组大鼠心肌组织,检测线粒体丙二醛(MDA)含量,MnSOD活性及其肿胀程度;Western blotting检测胞浆中细胞色素C(Cyt-C)、凋亡诱导因子(AIF)表达;比色法测定Caspase-3、Caspase-9蛋白酶的活性;流式细胞术测定心肌细胞凋亡情况。结果四逆汤组可以提高线粒体MnSOD的活性,减少MDA的含量及肿胀程度;有效抑制Cyt-C及AIF蛋白释放及Caspase-9和Caspase-3蛋白酶活性,减少凋亡的发生。结论线粒体在阿霉素性心衰发病中可能占有重要作用,四逆汤可能是通过减轻线粒体氧化损伤,减少心肌细胞凋亡来保护心肌组织。

Aim To investigate the protective effects of Sini decoction （SND） on mitochondrial mediated apoptosis in Adriamycin（ADR）-induced heart failure rats. Methods SD rats were randomly divided into three groups,eontrol group, heart failure group and SND group. ADR was injected in the rats of heart failure group and SND group by caudal vein. After injection,the rats in SND group were biven SND （3.75g/kg/d, p.o. ）. Three weeks later, cardiac function, activity of Mn SOD, content of malondialdehyde （MDA） and mitochondrial swelling were measured. Expression of Cyt-C and apoptosis indueing factor （AIF） were detected by Western blotting. Activity of caspase-3 and cCaspase-9 were quantified by spectrophotometer. Apoptosis in rate was determinated by flow cytometry. Results SND could increase the activity of Mn-SOD,decrease MDA content and mitochondrial swelling, decrease the activity of Caspase-3 and Caspase-9, decrease releasing of Cyt-C and AIF from mitochondria and cell apoptosis. Conclusion Mitochondria may play an important role in ADR-induced heart failure rats. SND can protect myocardial cell from apoptosis. The mechanism may be closely related to the protective effects of Sini decoeion on mitoehondria.