目的: 通过对胰岛素样生长因子结合蛋白相关蛋白1(IGFBPrP1)与硫代乙酰胺(TAA)对小鼠肝组织影响的研究,明确IGFBPrP1在肝纤维化中的作用及其机制.方法: 清洁级C57BL/6野生型小鼠32只,随机分为4组:正常对照组、重组小鼠IGFBPrP1(rmIGFBPrP1)4周组、TAA 2周组及TAA 4周组,每组8只.取肝组织行HE、苦味酸-天狼星红及免疫组织化学染色和Western blotting检测.结果: rmIGFBPrP1 4周组肝细胞广泛脂肪变性,TAA 2周组出现纤维组织增生,TAA 4周组病理改变较TAA 2周组严重.与正常对照组相比,rmIGFBPrP1 4周组、TAA 2周组和TAA 4周组IGFBPrP1、转化生长因子β1(TGF-β1)、Smad3、p-Smad2/3、Ⅲ型胶原(Col Ⅲ)、I型胶原(ColⅠ)、纤维连接蛋白(FN)的表达增高(P<0.05).rmIGFBPrP1 4周组IGFBPrP1、ColⅠ和FN的表达与TAA 2周组无显著差异.结论: IGFBPrP1在TAA诱导的肝纤维化形成过程中发挥重要作用,并可作为独立致病因子引起小鼠肝组织中细胞外基质生成增多,且该作用是通过TGF-β1/Smad3信号通路来实现的.
AIM : To investigate the effects of insulin - like growth factor binding protein related protein 1 ( IG- FBPrPI ) and thioacetamide (TAA) on the liver tissues, and to identify the role of IGFBPrP1 in liver fibrosis. METHODS: Thirty- two male C57BL/6 wild -type mice were randomly divided into 4 groups (n = 8 in each group) : control group, recombinant murine 1GFBPrP1 ( rmlGFBPrPI ) 4 weeks group, TAA 2 weeks group and TAA 4 weeks group. The methods of hematoxylin- eosin (HE) staining, picric acid- Sirius red staining, immunohistochemistry and Western blotting were performed. RESULTS: The extensive fatty degeneration of liver cells in rmIGFBPrP1 4 weeks group was observed. The collagen deposition was found in TAA 2 weeks group. In TAA 4 weeks group, the degree of hepatic fibrosis was more serious than that in TAA 2 weeks group. The expression levels of IGFBPrP1, transforming growth factor beta 1 (TGF- β1 ), Smad3, p- Smad2/3, collagen Ⅲ, collagen Ⅰ and fibronectin (FN) in liver tissues were higher in rmlG- FBPrP1 4 weeks group, TAA 2 weeks group and TAA 4 weeks group than those in control group. No significant difference of the expression levels of IGFBPrP1, collagen Ⅰ and FN between rmlGFBPrP1 4 weeks group and TAA 2 weeks group was observed. CONCLUSION: IGFBPrP1 plays an important role in the process of thioacetamide - induced liver fibrosis. Meanwhile, IGFBPrP1 induces excessive deposition of extracellular matrix through TGF - β1/patSmad3 hway.