促红细胞生成素对阿霉素性心肌病大鼠心肌Bax和Bcl-2表达的影响

Erythropoietin effect on myocardial Bax and Bcl-2 expression for doxorubicin-induced cardiomyopathy of rats

目的:观察凋亡相关蛋白Bax和Bcl-2在阿霉素(DOX)性心肌病大鼠心肌中的表达,探讨促红细胞生成素(EPO)保护阿霉素性心肌病大鼠的机制。方法:31只雄性Wistar大鼠随机分为对照组、DOX组和DOX+EPO组。药物干预4周后,观察各组大鼠一般情况,进行超声心动图和心肌病理学检查,采用免疫组化和RT-PCR检测Bax与Bcl-2的蛋白和mRNA表达水平。结果:DOX组大鼠符合阿霉素性心肌病表现,DOX+EPO组大鼠左心功能改善,心肌纤维化明显减少。与DOX组相比较,EPO治疗(DOX+EPO组)未能降低Bax蛋白和mRNA表达水平,但显著升高了Bcl-2的表达水平(P<0.05)。结论:EPO对阿霉素性心肌病具有良好的保护作用,这可能与其上调Bcl-2蛋白和mRNA表达有关。

Objective To determine apoptotic protein expression of Bax and Bcl-2 of myocardium in rats of doxorubiein （DOX）-induced cardiomyopathy, and to investigate protective mechanisms of erythropoietin （EPO） on DOX-induced cardiomyopathy. Methods Thirty-one Wistar rats were randomly divided into control group, DOX group and DOX ＋EPO group. After four weeks of drugs treatment, all rats were evaluated for general situation, echocardiography and histological analysis. Protein and mRNA expression of Bax and Bcl-2 were detected by immunohistochemistry and reverse transcription-polymerase chain reaction （RT-PCR） respectively. Results There were 75% of rats with obvious ascites in DOX group. Rats in DOX group showed similar changes to those of DOX induced-cardiomyopathy in human by echocardiography and histological analysis. There was a significant improvement in cardiac function and myocardial fibrosis in DOX＋EPO group compared to DOX group. Immunohistochemistry and RT-PCR revealed that compared to the DOX group, treatment with EPO did not decrease Bax protein and mRNA expression, but significantly increase Bcl-2 expression. Conclusions EPO may exert protective effects on DOX- induced cardiomyopathy, which may attribute to up-regulation of protein and mRNA expression of Bcl-2.