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

摘要

Objective To determine apoptotic protein expression of Bax and Bcl-2 of myocardium in rats of doxorubicin ( 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.%目的:观察凋亡相关蛋白Bax和Bc1-2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Bc1-2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Bc1-2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Bc1-2蛋白和mRNA表达有关.