中药肝炎平对CCl_4诱导的肝纤维化大鼠TGFβ_1/Smad信号通路的影响  

Effects of traditional Chinese medicine Ganyanping on TGFβ_1/ Smad signaling pathway in carbon tetrachloride-induced hepatic fibrosis of rats

作　　者：熊章鄂[1] 但自力[1] 唐望先[2] 严红梅 

机构地区：[1]华中科技大学同济医学院附属同济医院消化内科,湖北省武汉市430030 [2]华中科技大学同济医学院附属同济医院肝病研究所,湖北省武汉市430030 [3]武汉市第七人民医院肝病科,湖北省武汉市430071

出　　处：《世界华人消化杂志》2006年第2期152-157,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30440088

摘　　要：目的:研究中药肝炎平对CCl4诱导的大鼠肝纤维化肝脏TGFβ1及其受体TβR Ⅰ,TβR Ⅱ水平和 Smad3,Smad7及前胶原α2(Ⅰ)(Colla2)mRNA 表达的影响,探讨其抗纤维化的作用机制．方法:健康Wistar大鼠38R随机分为正常对照组(N组)、模型对照组(A组)以及肝炎平治疗组(B组)．N组每日以生理盐水10μL/g灌胃,A 组及B组用CCl4制备大鼠肝纤维化模型,B组 4wk后开始以肝炎平10μL/g灌胃给药,A组同时以生理盐水10μL／g灌胃,每日1次．9 wk 后处死大鼠,取肝组织作病理学检查,免疫组化检测TGFβ1及其受体TβR Ⅰ,TβR Ⅱ的表达, RT-PCR检测胞内信号蛋白Smad3,Smad7以及 Coila2 mRNA的表达．结果:与正常对照组相比,模型组TGFβ1、 TβR Ⅰ、TβRⅡ、Smad3、Colla2表达明显增强,Smad7表达明显下降．经肝炎平治疗后大鼠肝脏TGFβ1及其受体TβR Ⅰ,TβR Ⅱ表达均比模型组减弱(TGFβ1:4．30±0．16 vs 4．18 ±0．17．P<0．05;TβR Ⅰ:4．35±0．14 vs 4．24± 0．10．P<0．05;TβRⅡ:4.37±0．11 vs 4．27±0．08． P<0．05)．肝炎平同时下调Smad3和Colla2 mRNA的表达(Smad3:0．93±0．05 vs 0．90± 0．41．P<0．05;Colla2:0．95±0．03 vs 0．92±0．03． P<0．05),上调Smad7 mRNA的表达(0．84±0．05 vs 0．87±0．03,P<0．05)．另外,肝炎平组大鼠肝脏病理变化显著改善．结论:肝炎平对大鼠肝纤维化肝脏TGFβ1/ Smad信号通路有明显的影响,能抑制CCl4诱导的大鼠肝纤维化,其作用机制可能为抑制 TGFβ1．及其受体TβR Ⅰ,TβRⅡ蛋白表达,下调Smad3 mRNA,上调Smad7 mRNA的表达, 并最终下调了作为主要细胞外基质的Colla2 mRNA的表达．AIM： To study the effects of Ganyanping on the experimental hepatic fibrosis induced by carbon tetrachloride （CCl4） in rats, and to explore its anti-fibrotic molecular mechanism. METHODS： Thirty-eight healthy Wistar rats were randomly divided into normal control （N）, model control （A）, and Ganyanping therapeutic group （B）. The rats in group N was treated with normal saline by intragastrical irrigation, and those in group A and B were subcutaneo us injected with CCl4 to establish hepatic fibrosis model. Four weeks later, the animas in group B were treated with Ganyanping （10 μL/g） and those in group A were treated with normal saline by intragastrical irrigation at the same time. The histological changes of the liver tissues were examined by pathological examination. The protein expression of transforming growth factor beta 1 （TGFβ1） and its receptors （TβRⅠ and TβRⅡ were measured by immunohistochemical technique. The changes of Smad3, Smad7 and Colla2 mRNA expression were observed by reverse transcription polymerase chain reaction （RT-PCR）. RESULTS： The levels of TGFβ1, TβRⅠ, TβRⅡ, Smad3 and Colla2 expression were elevated, and that of Smad7 was reduced in the model rats. In comparison with those in group A, the levels of TGFβ1 and its receptors protein expression in group B were significantly decreased after treatment with Ganyanping （TGFβ1： 4.18 ± 0.17 vs 4.30 ± 0.16, P 〈 0.05; TβR Ⅰ ： 4.24 ± 0.10 vs 4.35 ± 0.14, P 〈 0.05; TβR Ⅱ ： 4.27 ± 0.08 vs 4.37 ± 0.11, P 〈 0.05）. Meanwhile, the levels of Smad3 and Colla2 mRNA expression were also downregulated （Smad3：0.90 ± 0.41 vs 0.93 ± 0.05, P 〈 0.05; Colla2：0.92 ± 0.03 vs 0.95 ± 0.03, P 〈 0.05）. However, the level of Smad7 mRNA expression was significantly up-regulated （0.87 ± 0.03 vs 0.84 ± 0.05, P 〈 0.05）. The pathological changes of liver tissues in group B were also markedly alleviated. CONCLUSION： Ganyanping has significant inhibitory effects on CCl4-induced h

关 键 词：肝炎平 TGFβ1/Smad信号通路 肝纤维化 

分 类 号：R285.5[医药卫生—中药学]