血管紧张素Ⅱ受体拮抗剂对大鼠肝纤维化的疗效及作用机制  

Effect of valsartan on expression of TGF-β1 and TGFRⅡmRNA in experimental hepatic fibrosis in rats

作　　者：龚作炯[1] 宋仕玲[1] 黄砚青[1] 阮鹏[1] 张志荣[1] 

机构地区：[1]武汉大学病毒学教育部重点实验室,武汉大学人民医院感染科,430060

出　　处：《肝脏》2004年第2期97-100,共4页Chinese Hepatology

摘　　要：目的　观察血管紧张素Ⅱ受体拮抗剂缬沙坦抗四氯化碳诱导大鼠肝纤维化的疗效及可能作用机制。方法　将 80只Wistar大鼠随机分为 4组 ,每组 2 0只 ,A组为正常对照组 ,B组为肝纤维化模型组 ,C、D组分别为缬沙坦早期治疗组和治疗组。B、C、D组大鼠均给四氯化碳 ( 1次 /3d ,共 8周 )诱导肝纤维化 ,C、D组大鼠分别于第 1、4周予以缬沙坦 ( 2 0mg/kg ,每天 1次 )灌胃治疗 ,所有大鼠于第 8周处死。RT PCR检测大鼠肝组织转化生长因子 (TGF) β1与其受体(TGFR)ⅡmRNA ,免疫组化技术检测TGF β1在肝内的表达及定位 ,肝组织H E染色及电镜检测病理改变 ,放射免疫法检测血清透明质酸 ,生化技术检测肝功能变化。结果　与B组大鼠比较 ,RT PCR显示经缬沙坦治疗 ,C、D组大鼠肝内TGF β1与TGFRⅡmRNA表达明显降低 ,免疫组化检测显示肝组织TGF β1表达明显减少 (P <0 .0 1) ,TGF β1的免疫阳性反应信号主要位于纤维间隔中的细胞质。大鼠肝组织TGF β1在C组与D组表达间比较差异有显著性 (P <0 .0 5 )。经缬沙坦治疗后 ,肝纤维化大鼠肝小叶结构趋于正常 ,纤维间隔明显变薄 ,血清透明质酸酶明显降低 (P <0 .0 5 ) ,肝功能好转 (P <0 .0 5 )。结论　缬沙坦能有效地减轻肝纤维化大鼠的肝脏损伤及纤维化程度 。Objective To assess the effects of an angiotensin Ⅱ type 1 (AT1) receptor antagonist, valsartan on hepatic fibrosis induced by carbon tetrachloride (CCl 4) in rats and to investigate the expression of transforming growth factor beta l (TGF β1) and TGF β receptor Ⅱ(TGFRⅡ) mRNA on liver tissues. Methods 80 Wistar rats were randomly allocated into four groups: group A: healthy controls, group B: hepatic fibrotic models induced by CCl 4, group C and D: models administrated orally with valsartan starting at the first and fourth week after rats exposure to CCl 4. Except for group A, rats were subcutaneously injected CCl 4 (once every three days for eight weeks). Rats in two treatment groups were also given valsartan of 20mg/kg daily via gastrogavage. All rats were sacrificed at the eighth week, blood and liver were collected for assays. The effects of valsartan on hepatic fibrosis were evaluated of the expression of TGF β1 and TGFRⅡmRNA by RT PCR. The expressions and sites of TGF β1 protein in liver tissue were studied by an immunohistochemical staining. The serum hyalauronic acid (HA) and liver functioin were examined by radioimmunoassay (RIA) and biochemsitry. The liver histopathology was examined by H E staining. Results Compared with group B, the liver level of TGFβ1,TGFRⅡ mRNA and the expression of TGFβ1, serum HA content in group C and D were significantly reduced by valsartan treatment ( P <0.05 or P <0.01). Liver function was also improved by valsartan treatment ( P <0.01). There was significant differentce between group C and D ( P <0.05). In contrasted with model groups, liver fibrosis as assessed by histology ( P <0.01) was considerably attenuated by valsartan treatment. Conclusion Valsartan, an AT1 receptor antagonist, may act as a potent anti fibrotic drug to inhibit hepatic fibrosis in rats induced by CCl 4. The mechanisms of valsartan anti fibrosis appear to associate with their effects of down regulating TGF β1 and TGFRⅡ mRNA and the expressio

关 键 词：肝纤维化 血管紧张素Ⅱ受体拮抗剂 转化生长因子 转化生长因子受体 

分 类 号：R575.2[医药卫生—消化系统]