氯沙坦对大鼠慢性心力衰竭的干预作用

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-2 χ² =6.81、P =0.0074；Bax χ² =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。

Losartan intervenes chronic heart failure of rats

Objective To study the reasons and mechanism of cardiomyocyte apoptosis in chronic heart failure by using Losartan and to provide a theoretical basis for the treatment of chronic heart failure. Methods The models of chronic heart failure were produced by injecting Adriamycin and Losartan as intervention agents, the expression of apoptotic protein Bax, Bcl-2 and channel protein ERK1, JNK1 and P38MAPK were detected by immunohistochemistry and RT-PCR.Cardiomyocyte apoptosis and myocardial ultrastructure are detected by transmission electron microscopy and TUNEL staining.Results Compared with the model group of heart failure, after Losartan treatment, the ultra structure of myocardial cells were significantly improved, Apoptosis index was decreased significantly (P <0.01), The level of Bax and JNK1 decreased (Bax χ~2=6.6149, P=0.0078; JNK1 q=22.0156,P<0.01). However, the expressions of ERK1 and Bcl-2 were significantly increased (ERK1 q=15.3514,P<0.01;Bcl-2 χ~2=6.81,P=0.0074).Conclusion The effect of Losartan on chronic heart failure is related closely with the pathway of ERK1 and JNK1, and no p38 MAPK pathway.