氯沙坦对实验性肝纤维化模型大鼠的作用

Effect of losartan on the rat model of experimental hepatic fibrosis

目的研究氯沙坦对40%CCL4诱导的大鼠肝脏纤维化的影响。方法制备CCL4诱导的大鼠肝纤维化模型,同时给予氯沙坦灌胃,共6周,分别取血和肝组织,检测血清天冬氨酸转氨酶(AST)、丙氨酸氨基转移酶(ALT);光镜下观察肝组织病理改变;偏光显微镜下观察肝组织纤维化的程度;免疫组化检测Ⅰ、Ⅲ型胶原的表达;检测大鼠肝组织中AngⅡ、AT1R mRNA表达。结果与模型组比较,氯沙坦干预组炎症反应、纤维化程度明显减轻,Ⅰ、Ⅲ型胶原的表达明显减少(P<0.05),肝功能改善;肝组织中AngⅡ、AT1R mRNA表达降低(P<0.05)。结论氯沙坦可能通过降低AngⅡ、AT1R的表达,而对CCL4诱导的大鼠肝纤维化起到一定的保护治疗作用。

Objective To explore the effect of angiotensin Ⅱ receptor blocker losartan on rats hepatic fibrosis induced by carbon tetrachloride （CCL4）. Methods Hepatic fibrosis was induced in rats by intraperitoneal injection of carbon tetrachloride（40%）. Meanwhile, losartan was given to the fibrosis＋losartan intervention group rats（daily gavage）, and sterile saline was given to the control rats for 6 weeks. Blood and liver tissue samples were taken for detecting aspartate aminotransferase （AST） and alanine aminotransferase （ALT）.The pathological changes and fibrosis extent of liver tissues were observed by light microscope and polarizing microscope respectively. Collagen type I and collagen type Ⅲ were detected by immunohistochemistry.Liver AngⅡ and AT1R mRNA expressions were determined by RT-PCR. Results Compared with those of the model group, liver inflammation and hepatic fibrosis were significantly reduced in the fibrosis＋losartan intervention group;collagen type I and collagen type Ⅲ content were lowered in the fibrosis＋losartan intervention group（P〈0.05）; the liver function was improved significantly.Meanwhile,the levels of AngⅡand AT1R mRNA in liver tissues also decreased（P〈0.05）. Conclusion Losartan may has a therapeutic effect on carbon tetrachloride-induced liver fibrosis rats by reducing the expressions of liver AngⅡand AT1R.