抗IGFBPrP1抗体对小鼠肝纤维化的预防作用及其机制的研究  

Preventive effects of anti-IGFBPrP1 antibody on hepatic fibrosis in mice

作　　者：陈丽霞[1] 刘立新[1,2,3] 张海燕[1,2,3] 张骞骞[1,2,3] 

机构地区：[1]山西医科大学第一医院科研实验中心,山西太原030001 [2]山西医科大学肝病研究所,山西太原030001 [3]山西医科大学省部共建教育部细胞生理学重点实验室,山西太原030001

出　　处：《中国病理生理杂志》2010年第11期2185-2190,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30871146);教育部新世纪优秀人才支持计划资助项目(No.NCET-06-0264)

摘　　要：目的:明确抗胰岛素样生长因子结合蛋白相关蛋白1(IGFBPrP1)抗体能否预防硫代乙酰胺(TAA)诱导的小鼠肝纤维化的形成,同时探讨其机制。方法:将24只雄性C57BL/6野生型小鼠随机分为正常对照组、TAA4周组和TAA+抗IGFBPrP1抗体4周组,每组8只,观察肝组织形态学改变,免疫组织化学染色和Western blotting检测肝组织中α-平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)、Smad3、磷酸化Smad2/3(p-Smad2/3)、纤维连接蛋白(FN)、Ⅰ、Ⅲ型胶原(collagenⅠ、Ⅲ)及IGFBPrP1的表达。结果:TAA4周组肝损伤严重,α-SMA、TGF-β1、Smad3、p-Smad2/3、FN、collagenⅠ、Ⅲ及IGFBPrP1的表达明显高于正常对照组(P<0.01),TAA+抗IGFBPrP1抗体4周组肝损伤减轻,上述各指标表达均低于TAA4周组(P<0.01)。IGFBPrP1与TGF-β1、Smad3、p-Smad2/3、FN及collagenⅠ的表达呈正相关(P<0.01)。结论:抗IGFBPrP1抗体可预防TAA诱导的小鼠肝纤维化的形成,其机制为抑制肝星状细胞的活化和减少细胞核内p-Smad2/3的表达、抑制TGF-β1/Smad3信号通路,进而导致细胞外基质在肝组织中沉积减少。AIM： To investigate the preventive effect and mechanism of anti-insulin-like growth factor binding protein related protein 1（IGFBPrP1） antibody on hepatic fibrosis induced by thioacetamide （TAA） in mice.METHODS： Twenty-four male C57BL/6 wild-type mice were randomly divided into 3 groups （n= 8 in each group）： normal control group, TAA group （4 weeks） and TAA＋anti-IGFBPrP1 antibody group （4 weeks）. The morphological changes of liver tissues were observed. The expression levels of α-smooth muscle actin （α-SMA）, transforming growth factor beta 1 （TGF-β1）, Smad3, phosphorylated Smad2/3 （p-Smad2/3）, fibronectin （FN）, collagen I, collagen Ⅲ and IGFBPrP1 were detected by the methods of immunohistochemistry and Western blotting.RESULTS： In TAA group （4 weeks）, obvious injury of liver was observed, and the expression levels of α-SMA, TGF-β1, Smad3, p-Smad2/3, FN, collagen Ⅰ, collagen Ⅲ and IGFBPrP1 were significantly increased as compared with normal control group （P〈0.01）. Compared with TAA group （4 weeks）, the injury of the liver was alleviated and the expression levels of the proteins above were decreased in TAA＋anti-IGFBPrP1 antibody group （4 weeks, P〈0.01）. IGFBPrP1 was positively correlated with TGF-β1, Smad3, p-Smad2/3, FN and collagen I （P〈0.01）. CONCLUSION： Anti-IGFBPrP1 antibody prevents TAA-induced hepatic fibrosis in mice by inhibiting the activation of hepatic stellate cells, reducing the expression of p-Smad2/3 and inhibiting the TGF-β1/ Smad3 signal transduction, thereby depressing the deposition of extracellular matrix in liver tissues.

关 键 词：肝硬化 抗胰岛素样生长因子结合蛋白相关蛋白1抗体 细胞外基质 转化生长因子β SMAD3 

分 类 号：R363[医药卫生—病理学]