氯沙坦抗鼠肝纤维化的实验研究

摘要

[Objective] To study the expression of Smad2/3, Smad7, TIMP-1 and TGF-β1 in hepatic fibrosis induced by the exposure of CCL4 and the effects of Losartan on them. [Methods] A total of 40 healthy Wistar rats were divided into four groups randomly: control group, model group, prevention group and treatment group. Hepatic fibrosis models were established in latter 3 groups by injection CCL4. Liver tissue sections were stained with Hematoxylin-eosin and van Gieson to evaluate the degree of inflammation and hepatic fibrosis. The expression of Smad2/3, Smad7, TIMP-1 and TGF-β1 were measured by immunohistochemical staining in liver tissue. [Results] The degree of inflammation and hepatic fibrosis in model group was higher than that in control group, prevention group and treatment group. The expression of Smad2/3, TIMP-1 and TGF-β1 in model group was stronger than that in prevention group and treatment group (Smad2/3: 2.60±0.35, 1.09±0.28, 1.32±0.23; TIMP-1: 2.51±0.39, 1.69±0.42, 1.90±0.59; TGF-β1: 2.72±0.36, 1.65±0.31, 2.04±0.42; respectively), P＜0.05. The expression of Smad7 in model group was weaker than that in prevention group and treatment group (0.47±0.26, 2.50±0.35, 2.21±0.59, respectively), P ＜0.05. There were no differences on the expression of them between prevention group and treatment group, P ＞0.05.[Conclusion] Losartan may play a important role in attenuating the progression of rat hepatic fibrosis by inhibiting expression of Smad2,3 TIMP-1, TGF-β1 and promoting expression of Smad7.%目的 探讨CCL4诱导的肝纤维化模型鼠肝组织Smad2/3,Smad7,TIMP-1,TGF-β1的表达及氯沙坦干预后对其表达的影响.方法 Wistar大鼠40只,随机分成正常对照组、模型组、氯沙坦预防组和治疗组,采用CCL4皮下注射构建肝纤维化模型.行HE和VG染色,判断肝组织炎症和纤维化的程度.免疫组化方法检测各组Smad2,3 Smad7和TIMP-1,TGF-β1的表达.结果 氯沙坦预防组和治疗组的肝组织炎症和纤维化程度明显低于模型组;Smad2,3 TIMP-1 TGF-β1在氯沙坦预防组和治疗组的阳性表达均低于模型组(分别为Smad2,3:1.69±0.42,1.90±0.59,2.51±0.39; TIMP-1:1.09±0 28,1.32±0.23,2.60±0.35;TGF-β1:1.65±0.31,2.04±0.42,2.72±0.36),P＜0.05;Smad7在氯沙坦预防组和治疗组的阳性表达高于模型组(分别为2.50±0.35,2.21±0.59,0.47±0.26),P＜0.05.Smad2,3 Smad7 TIMP-1和TGF-β1在氯沙坦预防组和治疗组的表达差异无显著性,P＞0.05.结论 氯沙坦抗肝纤维化作用可能与抑制TGF-β1,TIMP-1,Smad2,3和促进Smad7的表达有关.