HSC的活化、增殖与TGF-β_1及其Ⅰ型受体在中晚期纤维化肝组织中的改变及护肝片对其的影响  

THE ACTIVATION AND PROLIFERATION OF HSCs AND THE ALTERED EXPRESSION OF TRANSFORMING GROWTH FACTOR BETA-1 AND ITS TYPE Ⅰ RECEPTOR IN THE MIDDLE AND LATE STAGE OF RAT HEPATIC FIBROSIS AND THE EFFECT OF LIVER-AID TABLETS ON THEM

作　　者：吴义春[1] 吴强[2] 杨雁[2] 杨枫[2] 陈敏珠[2] 

机构地区：[1]安徽医学高等专科学校,合肥230061 [2]安徽医科大学,合肥230022

出　　处：《中国组织化学与细胞化学杂志》2007年第1期80-86,共7页Chinese Journal of Histochemistry and Cytochemistry

基　　金：安徽省自然科学研究基金(99044126);安徽省教育厅自然科学研究重点项目(2006KJ092A)

摘　　要：目的探讨护肝片对中、晚期纤维化大鼠肝组织肝星状细胞(HSC)的活化与增殖及转化生长因子-β1(TGF-β1)及其Ⅰ型受体(TβRⅠ)表达的影响。方法采用12.5%CCl4诱导的大鼠肝纤维化模型,自造模之日起,大鼠分组灌胃给药(护肝片921mg.kg-1)或溶媒,每日一次,直至8或13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α-平滑肌肌动蛋白(α-SMA)、TGF-β1及TβRⅠ蛋白的表达,并用MetaMor-ph图像分析系统计数α-SMA阳性细胞数、对TGF-β1及TβRⅠ蛋白表达量进行定量分析。结果1.模型复制8周和13周,模型组的肝损伤及其纤维化分级均明显高于正常组(P<0.01),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13周,模型组活化的HSC(即α-SMA阳性细胞)数量较正常组明显增多、TGF-β1及TβRⅠ蛋白的表达较正常组明显增强(P<0.01);3.护肝片显著抑制8、13周纤维化肝组织HSC的活化与增殖和TGF-β1及TβRⅠ蛋白的表达(P<0.01)。结论抑制HSC的活化与增殖和TGF-β1及TβRⅠ的表达可能是护肝片抗肝纤维化作用的靶点之一。Objective To study the effect of Liver-aid tablets on the activation and proliferation of hepatic stellate cells （HSCs） and on the protein expression of transforming growth factor beta-1 （TGF-β1） and its type Ⅰ receptor （TβRⅠ ） in the middle and late stage of rat hepatic fibrosis. Methods SD rats were divided into three groups： normal control, model control and group of Liver-aid tablets. CC14 （12. 5%, 4ml·kg^-1） was injected sub-cutaneously in model rats twice a week for 8 and 13 weeks. The drug （921mg· kg^-1 in the group of Liver-aid tablets, but 0. 5% CMC-Na in control groups） was given intragastricly once a day for 8 and 13 weeks. The rats were killed at the end of 8th and 13th week respectively, and the left liver tissue was then used to make tissue microarrays （TMA）. The TMA sections were used for immunohistochemistry （IHC） to detect the protein expression of a-smooth muscle action （α-SMA）, TGF-β1 and TβRⅠ. The TGF-β1 and TβRⅠresults of IHC were quantified by MetaMorph imaging analysis system. Results 1. During 8 and 13 weeks, the degrees of liver injury and .fibrosis grades in the model group were higher than those in the normal group （P〈0.01）, which was ameliorated remarkably by Liver-aid tablets. 2. The number of activated HSCs in fibrotic model liver tissue was more than that in the normal group during 8 and 13 weeks （P〈0. 01）, and the protein expression of TGF-β1 and TβRⅠ in the model group was stronger than that in the normal group during 8 and 13 weeks （P〈0. 01）. 3. Liver-aid tablets inhibited the activation and proliferation of HSCs and the protein expression of TGF-β1 and TβRⅠ of fibrotic liver tissue during 8 and 13 weeks （P〈0. 01）. Conclusion Liver-aid tablets have anti-fibrosis effects on CC14-induced rat liver fibrosis, which might be performed through the pathway of inhibiting the activation and proliferation of HSCs and the expression of TGF-β1 and TβRⅠ.

关 键 词：肝硬化 护肝片 肝星状细胞 转化生长因子-β1 转化生长因子-βRⅠ 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]