四逆汤对阿霉素性心衰的治疗作用及其机制探讨

Protective Effects of Sini Decoction on Adriamycin-induced Heart Failure and its Mechanism

目的:探讨四逆汤在阿霉素(ADR)诱导的心力衰竭中的心肌保护作用及其可能的机制。方法:SD大鼠随机分为正常对照组、模型组及四逆汤组,模型组与四逆汤组大鼠尾静脉注射ADR复制心衰模型,四逆汤组给予四逆汤煎剂灌胃,其生药含量为3.75 g/(kg·d),实验结束时留取各组大鼠心肌组织,以免疫组化法测定心肌组织Bcl-xl蛋白及Bid蛋白表达情况,RT-PCR法检测Bcl-xl/Bcl-xs基因表达情况,流式细胞术测定心肌细胞凋亡情况。结果:与正常对照组比较,模型组大鼠心肌组织Bcl-xl蛋白的阳性反应物显著减少,Bid蛋白的阳性反应物显著增多,RT-PCR结果表明模型组Bcl-xl与Bcl-xs基因表达的比值与正常对照组比较显著下降,心肌细胞凋亡增多:而应用四逆汤后Bcl-xl蛋白阳性反应物表达显著上调,Bid蛋白表达下降,凋亡减少,Bcl-xl和Bcl-xs基因表达的比值则接近正常对照组。结论:Bcl-xl在阿霉素所导致的心衰发病中可能占有重要作用,四逆汤可能是通过上调抑凋亡因子Bcl-xl的表达,下调促凋亡因子Bcl-xs和Bid的表达来保护心肌细胞的。

Objective：To investigate the protective effects of Sini decoction（SND） on Adriamycin-induced heart failure and its mechanism.Methods：SD rats were randomly divided into three groups：control group,heart failure model group and SND group.ADR was injected in to the rats of model group and SND group by caudal vein.After injection,the rats in SND group were given SND[3.75 g/（kg·d）,p.o.].Three weeks later,protein expressions of Bid and Bcl-xl were detected by immunohistochemistry：mRNA expression ratio of Bcl-xl/Bcl-xs was detected by RT-PCR and apoptosis rate was determinated by flow cytometry.Results：Compared with control group,the protein expression of Bcl-xl and mRNA ratio of Bcl-xl/Bcl-xs obviously decreased,while the protein expression of Bid and apoptosis rate significantly increased in the model group.SND could decrease cell apoptosis,increase the protein expression of Bcl-xl,increase bcl-xl/bcl-xs mRNA ratio and decrease Bid protein expression.Conclusion：Bcl-xl may play an important role in ADR-induced heart failure rats.The mechanism of SND on protecting cardiocyte may be related to apoptosis correlation factor,Bcl-xl and Bid.