护肝片对纤维化肝组织TGF-β_1表达的抑制作用  

Effect of Liver-aid Tablet on Expression of Transforming Growth Factor Beta-1 in Rat Hepatic Fibrosis

作　　者：吴义春[1] 吴强[1] 杨雁[2] 杨枫[1] 陈敏珠[2] 刘琛[3] 

机构地区：[1]安徽医科大学病理学教研室,安徽合肥230032 [2]安徽医科大学临床药理研究所 [3]安徽中医学院中西医结合系

出　　处：《安徽中医学院学报》2004年第3期40-43,F002,共5页Journal of Anhui Traditional Chinese Medical College

基　　金：安徽省自然科学研究基金项目 (990 4 4 1 2 6 )

摘　　要：目的 :探讨护肝片对中、晚期纤维化肝组织转化生长因子 β1(TGF β1)蛋白及mRNA表达的影响。方法 :采用 1 2 5 g/LCCl4 诱导的大鼠肝纤维化模型 ,自模型复制之日起 ,大鼠分组灌胃给药 (护肝片 92 1mg/kg)或溶媒 ,每日 1次 ,直至 8,1 3周末 ,分别处死动物 ,取左叶肝组织石蜡包埋 ,制作组织芯片。免疫组化S P法检测大鼠肝组织TGF β1蛋白的表达 ;原位杂交检测TGF β1mRNA的表达。用MetaMorph图像分析系统对TGF β1蛋白及mRNA的表达量进行定量分析。结果 :①模型复制 8周和 1 3周 ,模型组的肝损伤及其纤维化分级均明显高于正常组 (P<0 .0 1 ) ,护肝片组的肝损伤及其纤维化分级均轻于模型组。②模型复制 8周和 1 3周 ,模型组TGF β1及mRNA的表达均较正常组显著增多 (P <0 .0 1 ) ;且其蛋白和mRNA的表达相互间呈显著正相关 (P <0 .0 1 )。③护肝片显著抑制 8,1 3周纤维化肝组织TGF β1蛋白及mRNA的表达 (P <0 .0 1 )。结论 :护肝片可减轻肝组织的损伤及其纤维化程度 ,它可能在蛋白及mRNA双重水平上抑制TGF β1的表达 ,从而发挥抗肝纤维化作用。Objective:To study the effect of Liver aid Tablet on protein and mRNA expression of transforming growth factor beta 1(TGF β 1) in rat hepatic fibrosis.Method: SD rats were divided into three groups:normal control,model control and group of Liver aid Tablet.CCl 4(125 g/L,4 ml/kg)was injected sub cutaneously in rat twice a week for 8,13 weeks respectively.The drug(921 mg/kg,but 5 g/L CMC Na in control groups)was given intragastricly once daily for 8,13 weeks respectively.The rats were killed at the end of 8 th and 13 th week respectively,the left liver tissue was then employed to make tissue microarrays(TMA).The TMA sections were used for immunohistochemistry(IHC)and in situ hybridization(ISH)to detect the protein and mRNA expression of TGF β 1.The results of IHC and ISH were quantified by MetaMorph imaging analysis system.Result: ① During 8 and 13 weeks,the degrees of liver injury and fibrosis grades of hepatofibrotic rat liver induced by CCl 4 of model groups were higher than those in normal groups (P<0.01),which were ameliorated remarkably by Liver aid Tablet.②The protein and mRNA expression of TGF β 1 in fibrotic model liver tissue was stronger than that in normal group during 8 and 13 weeks(P<0.01).The protein and mRNA expression of TGF β 1 was positively correlated to each other during 8 and 13 weeks(P<0.01). ③ Liver aid Tablet inhibited the protein and mRNA expression of TGF β 1 of fibrotic liver tissue in rats during 8 and 13 weeks(P<0.01).Conclusion: Liver aid Tablet have anti fibrosis effects on CCl 4 induced rat liver fibrosis,which might be through the pathway of inhibiting the expression of TGF β 1 at both protein and mRNA levels.

关 键 词：肝纤维化 护肝片 转化生长因子-Β1 免疫组织化学 原位分子杂交 组织芯片 

分 类 号：R572.2[医药卫生—消化系统] R285.5[医药卫生—内科学]