摘要
目的观察缬沙坦预防、治疗大鼠肝纤维化的作用和机制。方法雄性SD大鼠30只,随机分为3组:缬沙坦预防组(A组),模型组(B组),缬沙坦治疗组(C组)。二甲基亚硝胺(DMN)腹腔注射,各组每周连续3d,1;L/d,共4周。A组造模同时给于缬沙坦10mg/(kg·d)灌胃,共4周,第5周起停止腹腔注射DMN后仍按原剂量灌胃,再4周。C和B2组停止造模后,分别给予缬沙坦10mg/(kg·d)或生理盐水灌胃,共4周。8周后留取肝标本,行HE染色和Masson染色,以免疫组化法检测a-平滑肌肌动蛋白(a—SMA)含量。结果(1)A组:肝索排列基本整齐,有少量出血,汇管区稍扩大,未见胶原纤维增生。B组:肝组织大片出血坏死,有假小叶形成。c组:肝索排列紊乱,有出血坏死,汇管区扩大,有纤维间隔伸向肝小叶。(2)Masson染色胶原定量分析:B组明显高于A、C2组(P〈0.01),A组低于C组(P〈0.05)。(3)肝窦壁a—SMA观察:c组肝窦壁强阳性表达,A组肝窦壁基本不表达,仅见于汇管区,B组肝窦壁阳性表达,3组定量差异有统计学意义(P〈0.05)。结论在DMN诱导的肝纤维化模型中,缬沙坦部分通过抑制肝星状细胞(HSC)的活化预防和治疗肝纤维化,且预防效果优于治疗。
Objectives The purpose of this study is to observe the effects of valsartan on hepapatic fibrosis. Methods Thirty male Sprague-Dawley rats were randomly divided into three groups: valsartan -prevetive group (A), modle group of hepatic fibrosis (B)and valsartan -treating group (C). The model of hepatic fibrosis in rats was induced by intraperitoneal injection of dimethylnitrosamine (DMN) for 4 weeks (2ml/kg everyday, three times a week). Valsartan ( 10mg/kg everyday) was given together with injection of DMN per intragastric (Ig) in group A for 8 weeks. After stop injection of DMN, the S valsartan( 10mg,/kg, everyday)was given per Ig in group C for 4 weeks: After modeling, normal saline were given per Ig everyday in group B. At the end of eighth week, the histomorphylogic structure of the liver was observed with light microscope. Immunohistochemical staining was used to evaluate the expression of a-SMA. Results In group B, there was a large necrotic area and a number of pesudolobes appeared in the liver tissue. In group A, there were normal hepatic cords. In the group C, there was fibrosis interval formation and portal area expansion and fibrotic intervals extending to the lobule. The quantitative analysis of Masson staining showed that the collagen quantities in group B was higher than that of other group( P 〈0. 01 ). The collagen quantities in group A was lower than that of group C ( P 〈 0. 05 ). The results of immunohistochemical staining showed that the expression of aSMA in group B was strong positive, middle positive in group C, and weak positive in group A( P 〈 0. 05 ). Conclusion The valsartan has preventive and treatment effects on hepatic fibrosis in rats of hepatic fibrosis model induced by DMN, and the preventive effect of valsartan is better than its treatment effect. The valsartan can ameliorate the liver cirrhosis by partly suppressing the activation of HSC.
出处
《中国医师杂志》
CAS
2009年第2期185-187,共3页
Journal of Chinese Physician