双环醇对小鼠日本血吸虫病肝纤维化即早基因与TGF-β1、TIMP1及胶原表达的影响  

Effect of bicyclol on the expression of hepatic immediate early genes,TGF-β1,TIMP1 and collagen in liver tissues of mice infected with Schistosoma japonicum

作　　者：何生松[1] 徐标[1] 韩春荣[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院感染科,湖北省武汉市430022

出　　处：《世界华人消化杂志》2007年第35期3678-3684,共7页World Chinese Journal of Digestology

摘　　要：目的:研究双环醇对小鼠日本血吸虫病肝纤维化的治疗作用及其机制.方法:将80只小鼠随机分为4组,低剂量,高剂量治疗组和实验组各组小鼠感染日本血吸虫8 wk后,分别以60 mg/(kg·d)、120 mg/(kg·d)双环醇治疗8 wk以及不进行任何治疗,第4组小鼠作为正常对照组.应用HE染色、RT-PCR及免疫组化染色法,观察和分析不同剂量双环醇治疗前后各组小鼠肝组织病理改变和c-fos mRNA、c-jun mRNA、转化生长因子β1(transforming growth factorβ1,TGF-β1)、基质金属蛋白酶组织抑制因子1(tissue inhibitor of metalloproteinase 1,TIMP1)和Ⅰ、Ⅲ型胶原的表达变化.结果:高剂量双环醇治疗后肝纤维化组织病理损伤减轻,高剂量双环醇组TGF-β1、TIMP1和Ⅰ、Ⅲ型胶原含量(平均积分光密度)分别是0.1815±0.0231、0.2324±0.0536、0.1811±0.0514、0.1543±0.0603明显低于实验对照组0.2139±0.0134、0.2648±0.0361、0.2140±0.0271、0.1862±0.0217.而低剂量双环醇与实验对照组比较无显著差异.与实验对照组相比,高剂量双环醇组小鼠肝组织中c-fos mRNA,c-jun mRNA表达与实验对照组和低剂量双环醇组相比显著降低(c-fos mRNA:0.65 11±0.0551 vs 0.7844±0.0852.0.8072±0.0923:c-jun mRNA:0.6803±0.0712 vs 0.7982±0.0902.0.8289±0.094).结论:双环醇治疗血吸虫病肝纤维化作用呈剂量依赖性.高剂量双环醇抗血吸虫肝纤维化作用可能与其抑制肝组织即早基因表达、减少TGF-β1、TIMP1产生有关.AIM： To study the therapeutic effect of bicyclol on schistosome-infected mice with liver fibrosis and its mechanism. METHODS： Eighty mice were divided into four groups. Mice in the low-dose, high-dose and experimental control groups were infected with Schistosoma japonicum. After eight weeks, the low-dose and high-dose groups were treated with bicyclol at 60 mg （kg·d） and 120 mg （kg·d）, respectively, for 8 weeks. The experimental control group received no treatment. The fourth group was a normal control group. HE staining, RT- PCR and immunohistochemistry were used to observe the pathological changes in liver tissues of mice, the expression levels of hepatic c-fos and c-jun mRNAs, and the levels of hepatic transforming growth factor [β （TGF-β1）, tissue inhibitor of metaUoproteinase 1 （TIMP1）, and types I and III collagen, before and after treatment. RESULTS： Bicyclol treatment at a high dosage significantly relieved the degree of hepatic fibrosis compared with the experimental control group. The mRNA expression levels of c-los and c-jun in liver tissue were significantly reduced in the high-dose group compared with the experimental control and low-dose groups （c-fos mRNA： 0.6511 ± 0.0551 vs 0.7844 ± 0.0852, 0.8072 ± 0.0923; c-jun mRNA： 0.6803 ± 0.0712 vs 0.7982 ± 0.0902, 0.8289 ± 0.094）. The levels of hepatic TGF-β1, TIMP1 and types Ⅰ and Ⅲ collagen in the high-dose bicyclol treated group （integral light density： 0.1815 ± 0.0231, 0.2324 ± 0.0536, 0.1811 ± 0.0514, 0.1543 ± 0.0603） were significantly lower than those in the experimental control group （0.2139 ± 0.0134, 0.2648 ± 0.0361, 0.2140 ± 0.0271, 0.1862 ±0.0217）, but were still higher than those in the normal control group. CONCLUSION： The effect of bicyclol on liver fibrosis due to Schistosoma japonicum infection depend on its dosage. The anti-fibrotic effect of high-dose bicyclol treatment may be due to its inhibition on the expression of immediate early genes, which may lead to reduced synt

关 键 词：双环醇 日本血吸虫病 肝纤维化 即早基因 基质金属酶组织抑制因子 转化生长因子β1 逆转录聚合酶链式反应 

分 类 号：R575.2[医药卫生—消化系统]