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目的通过氯沙坦对慢性心力衰竭(慢性心衰)干预,研究慢性心衰时心肌细胞凋亡变化的原因及其机制,为慢性心衰的治疗提供理论依据。方法采用阿霉素制作慢性心衰大鼠模型,以氯沙坦为干预剂,采用透射电镜、免疫组织化学、RT-PCR及原位缺口末端标记法(TUNEL)对心肌细胞凋亡的形态和凋亡蛋白Bax、Bcl-2及通路蛋白细胞外信号调节激酶(ERK1)、氨基末端激酶(JNK1)和促分裂原活化蛋白激酶(P38MAPK)的mRNA表达变化进行研究。结果氯沙坦治疗后,与心衰组动物相比,心肌细胞的超微结构明显好转;凋亡指数明显降低(P<0.01);Bcl-2的含量明显升高而Bax的含量显著下降(Bcl-2χ2=6.81、P=0.0074;Baxχ2=6.6149、P=0.0078,均P<0.01);ERK1mRNA表达明显增加而JNK1mRNA表达则显著下降(q=15.3514,P<0.01;q=22.0156,P<0.01)。结论氯沙坦对慢性心衰的干预作用与ERK1和JNK1途径密切相关,而p38MAPK途径与此过程相关性不大。
Objective To investigate the causes of cardiomyocyte apoptosis in chronic heart failure and its mechanism by losartan intervention in chronic heart failure (CHF), so as to provide a theoretical basis for the treatment of chronic heart failure. Methods Adriamycin was used to make a rat model of chronic heart failure. Losartan was used as an intervention. The morphological changes and apoptosis of cardiomyocytes were observed by transmission electron microscopy, immunohistochemistry, RT-PCR and TUNEL. The changes of mRNA expression of Bax, Bcl-2, ERK1, JNK1 and P38MAPK were investigated. Results After losartan treatment, the ultrastructure of cardiomyocytes was significantly improved compared with those of heart failure group, and the apoptotic index was significantly decreased (P <0.01); the content of Bcl-2 was significantly increased and the content of Bax was significantly decreased Bcl-2χ2 = 6.81, P = 0.0074; Baxχ2 = 6.6149, P = 0.0078, all P <0.01); ERK1mRNA expression was significantly increased and JNK1mRNA expression was significantly decreased (q = 15.3514, P < ). Conclusion The intervention of losartan on chronic heart failure is closely related to the pathways of ERK1 and JNK1, while the path of p38 MAPK is not related to this process.