氯沙坦钾对5/6肾切除慢性心衰大鼠心脏的保护作用

研究氯沙坦钾对5/6肾切除慢性心衰大鼠心脏的保护作用及其机制。将大鼠随机分为假手术组、模型组、氯沙坦钾组，除假手术组外，其余大鼠通过5/6肾切除手术建立肾衰合并心衰模型。6周后，氯沙坦钾(50 mg/L)饮水给药两周。8周末处理大鼠，测定血流动力学、心指数、血清肌酐、尿素氮，PCR测定心脏CD133、VEGFR2、Sox2表达量变化，Western blot测定的心脏cleaved Caspase 3、Bcl-2的蛋白量变化。结果显示，氯沙坦钾能明显改善5/6肾切除大鼠的心脏结构功能:心指数降低，LVDP、LVEDP降低，LVSP升高；肾功能:血清肌酐、尿素氮含量降低，并且上调心脏CD133、VEGFR2、Sox2基因表达量，Bcl-2蛋白水平，下调cleaved Caspase-3蛋白水平。氯沙坦钾能够改善慢性心衰大鼠的心衰症状，其机制可能与动员骨髓干细胞，增加内皮祖细胞数量，修复内皮功能，抑制心肌细胞凋亡相关。

Protective effects of losartan potassium on 5/6 nephrectomy-induced chronic heart failure in rats

The purpose of this research is to investigate the therapeutic effects of losartan potassium on 5/6 nephrectomy rats with chronic heart failure(CHF)and to explore the mechanism. 24 Rats were randomly divided into three groups namely sham group(Sham), pathology group(Nx)and losartan potassium group(Lst), respectively. CHF model in rats were induced by 5/6 nephrectomy. At the 7th week, rats of Lst group were given losartan potassium(50 mg/L)for consecutive 2 weeks. Then all rats were measured for hemodynamic parameters, cardiac index, creatinine, urea nitrogen in serum, and expressions of CD133, VEGFR2, Sox2, cleaved Caspase-3 and Bcl-2 in heart. Compared with Nx group, rats of Lst group improved cardiac and renal functions: decreased LVDP, LVEDP, cardiac index, creatinine, urea nitrogen and increased LVSP. Furthermore, losartan potassium up-regulated gene expression of CD133, VEGFR2, Sox2 and protein level of Bcl-2, and down-regulated cleaved Caspase-3 protein expression. Results suggest that losartan potassium can improve cardiac function of rats with CHF which may be correlated with mobilizing bone marrow stem cells, increasing endothelial progenitor cells(EPCs)level in heart, repairing endothelial function, and inhibiting myocardial apoptosis.