肝星状细胞表达醛固酮合成酶基因及安体舒通抗肝纤维化的研究

CYP11B2 expression in rat liver and the efficacy of antisterone on liver fibrosis

目的 研究醛固酮合成酶基因－ＣＹＰ１１Ｂ２在大鼠肝组织中的表达与肝纤维化的关系及安体舒通抗肝纤维化的作用。方法 取雄性Ｗｉｓｔａｒ大鼠１２０只，随机分为３组，每组４０只。模型组：ＣＣｌ４油０．２５ｍｌ／１００ｍｇ皮下注射，３次／周；安体舒通组：ＣＣｌ４油注射的同时予以安体舒通２０ｍｇ·ｋｇ－１·ｄ－１灌胃，１次／日；对照组：橄榄油皮下注射。光镜下动态观察组织学改变，图像分析系统测量胶原面积。ＲＴ－ＰＣＲ和原位杂交检测ＣＹＰ１１Ｂ２的表达。结果 原位杂交及ＲＴ－ＰＣＲ显示ＣＹＰ１１Ｂ２表达定位于肝星状细胞胞浆，在纤维化形成时表达增强。第４周、６周，安体舒通组肝纤维化分级、胶原面积低于模型组（Ｐ＜０．０５）。第８周，安体舒通组与模型组相比差异无显著性意义（Ｐ＞０．０５）。结论 ＣＹＰ１１Ｂ２在纤维化肝脏的肝星状细胞中表达增强。安体舒通对早中期肝纤维化具有一定的治疗作用。

Objective:To identify aldosterone synthase gene-CYP11B2 mRNA expression in rat livers and evalu- ate the efficacy of antisterone. Methods One hundred and twenty male Wistar rats were divided into 3 groups: model group (subcutaneous injection of CCl4, 0.25 ml/100mg, 3 times/week), antisterone group (besides same dosage of CCl4 given, gastropufusion of antisterone of 20 mg .kg-1. d-1), and control group (subcutaneous injection of olive oil). The area of collagen was examined by image analyzing system. The expression of aldosterone synthase gene-CYP11B2 mRNA was detected by RT-PCR and in situ hybridization. Results The expression of CYP11B2 mRNA, which located in the endoplasm of HSC, was upregulated when fibrogenesis occurred. The grade of fibrosis and the area of collagen in antisterone group were less than those in mds group before 6 th week (P<0.05). After the 6 th week however, there was no signifcant difference between the two groups (P>0.05). Conclusions The expression of CYP11B2 mRNA is upregulated in fibrotic liver. Antisterone can partly have a fibrogenesis-inhibiting effect on the early stage of CC14-induced hepatic fibrosis.