摘要
背景:瘦素与肝纤维化的形成和发展有关,血管紧张素Ⅱ1型受体(AT1R)拮抗剂可降低大鼠脂肪组织瘦素的合成和分泌。目的:探讨AT1R拮抗剂缬沙坦对免疫性肝纤维化大鼠肝组织瘦素表达的影响。方法:36只Sprague-Dawley大鼠随机分为正常对照组、模型组和缬沙坦预防组,后两组腹腔注射猪血清建立肝纤维化模型,缬沙坦预防组大鼠于造模开始后每天予缬沙坦(30 mg/kg)灌胃。造模第10周处死大鼠,行HE染色和天狼猩红染色分析肝纤维化程度和胶原面积,以免疫组化法检测肝组织瘦素表达。结果:与正常对照组相比,模型组肝纤维化程度显著增强(P<0.05);胶原面积显著增多(10.08%±2.01%对0.62%±0.31%,P<0.01),肝组织瘦素表达显著增高(5.05+2.91对0.44±0.27,P<0.05)。经缬沙坦干预后,上述指标均显著改善。结论:瘦素可促进纤维化发生,AT1R拮抗剂缬沙坦能通过降低肝组织瘦素表达而延缓肝纤维化的发展,这可能是其抗纤维化机制之一。
Background： Leptin may be involved in the formation and development of liver fibrosis. Angiotensin Ⅱ type Ⅰ receptor （AT1R） antagonist can decrease the synthesis and secretion of leptin in adipose tissue in rats. Aims： To evaluate the effect of valsartan, an AT1R antagonist, on expression of leptin in rats with immunodamaged hepatic fibrosis. Methods： Thirty-six Sprague-Dawley rats were randomly divided into normal control group, model group and valsartan prevention group. In the latter two groups, liver fibrosis model was constructed by intraperitoneal injection with hog serum. Valsartan （30 mg/kg） was intragastrically administered daily after the construction of liver fibrosis in valsartan prevention group. At the 10th week, all the rats were sacrificed. The degree of fibrosis and collagen area were evaluated by HE and Sirius red staining. Expression of leptin was determined by immunohistochemistry staining. Results： As compared with normal control group, the degree of fibrosis （P〈0.05）, collagen area （10.08%±2.01% vs. 0.62%±0.31% , P〈0.01） and expression of liver tissue leptin （5.05±2.91 vs. 0.44±0.27. P〈0.05） were obviously increased in model group. After intervention with valsartan, all the above-mentioned indices significantly ameliorated. Conclusions： Leptin can induce liver fibrosis, and AT1R antagonist valsartan can delay the development of liver fibrosis via the reduction of leptin expression in liver tissue, which may be one of the mechanisms of its anti-fibrosis effect.
出处
《胃肠病学》
2009年第9期547-550,共4页
Chinese Journal of Gastroenterology
