【摘要】 目的探讨氯沙坦影响日本血吸虫病鼠早期肝纤维化的部分相关机制。方法将36只昆明小鼠随机分为正常对照组,感染对照组及氯沙坦组,采用日本血吸虫尾蚴35条/只鼠攻击感染小鼠建立血吸虫性肝纤维化模型,氯沙坦10 mg/(kg.d),灌胃,1次/d,连续6周,HE染色观察肝组织病理学改变;放射免疫法检测血清中透明脂酸(HA)含量,SP法检测α平滑机动蛋白(SMA),金属蛋白酸因子(TIMP)-1在肝组织中的表达;实时荧光定量法检测AT1R mRNA及转化生长因子β1(TGFβ1)mRNA的含量。结果氯沙坦组小鼠肝组织病理学改善明显;与感染组相比,氯沙坦组小鼠血清中HA含量降低,肝组织αSMA、TIMP-1的水平和AT1R mRNA、TGF1βmRNA的相对量均显著下降(P<0.05)。结论研究结果显示,氯沙坦改善肝组织病理学改变,降低血清中HA含量,与其能减少αSMA、TIMP-1的表达,下调AT1R mRNA、TGFβ1mRNA的水平有关。更多还原

【Abstract】 OBJECTIVE To study the part of the relevant mechanisms of losartan on hepatic fibrosis of mice infected with Schistosoma japonicum.METHODS Thirty-six kunming mice were randomly divided into three groups: the normal control group,the infectious control group and the test(losartan) group.Schistosomal liver fibrosis model was established by challenge with 35 cercariae S.japonicum.The test group was treated by losartan for 6 weeks.After 6 weeks of treatment,liver samples of the mice were obtained for observing the histopathological changes,the radioimmunoassay was used to detect the serum(HA) in hepatic fibrosis,the(SP) immunohistochemistry and image pro-plus 5.0 were applied to detect the expression of α(SMA),(TIMP)-1,and the real-time PCR was applied to detect the quantity of AT1R mRNA and transforming growth factor β1(TGFβ1) mRNA.RESULTS Compared with infectious control group,the liver histopathology was improved significantly.Losartan could significantly reduce(HA);and the levels of αSMA and TIMP-1 were degraded(P<0.05).The quantity of AT1R mRNA and TGFβ1 mRNA in losartan group was lower than that in infectious control group(P<0.05).CONCLUSIONS The losartan group can obviously improve liver histopathology,reduce serum HA.The possible reason is to markedly inhibit the expression of αSMA,TIMP-1,AT1R mRNA and TGFβ1 mRNA.更多还原