转化生长因子-β1疫苗对大鼠肝纤维化组织中胰岛素样生长因子结合蛋白的影响  

Study on effect of transforming growth factor-β1 vaccine on insulin-like growth factor binding protein in liver tissues of rats with liver fibrosis

作　　者：徐叶进[1] 陈凌[1] 陈海君[1] 付跃娟[1] 郭玉香[1] 盛棋跃[1] 陈永平[2] 

机构地区：[1]浙江省金华市中心医院感染内科,321000 [2] 温州医科大学附属第一医院感染内科

出　　处：《中华传染病杂志》2014年第7期385-390,共6页Chinese Journal of Infectious Diseases

基　　金：浙江省金华市科技局资助项目（2010-3-021）

摘　　要：目的：观察 TGF-β1疫苗干预对大鼠肝纤维化程度的影响，探讨其对肝纤维化组织中胰岛素样生长因子结合蛋白（IGFBP ）3、7的影响。方法20只大鼠用二甲基亚硝胺（DMN ）建立大鼠肝纤维化模型，其中10只 TGF-β1疫苗干预，另设10只作为正常对照组。6周末观察大鼠肝组织病理学变化，采用反转录-PCR 、免疫组织化学和 Western 印迹检测各组大鼠肝组织中 IGFBP3、IGFBP7的表达。数据行正态性检验和方差齐性分析，方差齐者采用 LSD 检验，计数资料采用 Fisher 确切概率法。结果肝组织病理学和血清 HA 、LN 均表明，TGF-β1疫苗干预可减轻大鼠肝纤维化程度。 IGFBP3 mRNA 在正常对照组、肝纤维化模型组、TGF-β1疫苗干预组大鼠肝组织分别为1．735±0．097、1．165±0．096和1．491±0．046（两两比较，t 值分别为4．575、6．285、8．489，均 P＜0．05）；IGFBP7 mRNA 分别为0．497±0．021、1．250±0．064和0．885±0．149（两两比较，t 值分别为5．161、30．101、7．250，均 P＜0．05）。免疫组织化学证实，IGFBP3在肝纤维化模型组、TGF-β1疫苗干预组较正常对照组大鼠肝组织中表达减少，IGFBP7的表达与 IGFBP3相反。 IGFBP3蛋白在正常对照组、肝纤维化模型组、TGF-β1疫苗干预组大鼠肝组织分别为7．508±0．357、5．200±0．210和5．751±0．178（两两比较，t 值分别为7．622、6．180、29．156，均 P＜0．05）；IGFBP7分别为1．176±0．051、1．735±0．115和1．428±0．056（两两比较， t值分别为7．188、4．827、8．649，均 P＜0．05）。结论 TGF-β1疫苗通过影响 IGFBP3、IGFBP7的表达，在肝纤维化的发生、发展过程中起重要作用。Objective To observe the effect of transforming growth factor-β1 （TGF-β1） vaccine on the degree of hepatic fibrosis in rats ,and to explore the effect of TGF-β1 vaccine on the insulin-like growth factor binding protein （IGFBP）3 and IGFBP7 .Methods The hepatic fibrosis rat model was set up by injecting N-nitrosodimethylamine . Among them , 10 rats were injected with TGF-β1 vaccine , and additional 10 rats were set up as healthy control group .Changes in hepatic pathology were observe and the expressions of IGFBP3 and IGFBP7 were detected by the methods of immunohistochemistry , reverse transcription polymerase chain reaction （RT-PCR） and Western blot in rat fibrosis tissues after 6 weeks . Normality test and analysis of variance were conducted .LSD test was conducted if variances were tested homogeneity .Categorical data were analyzed using Fisher exact test . Results Changes in hepatic histology and serum levels of hyaluronic acid and laminin suggested that TGF-β1 vaccine interventions could reduce the extent of hepatic fibrosis in rats .The expressions of IGFBP3 mRNA in control group ,hepatic fibrosis model group and vaccine intervention group were 1 .735 ± 0 .097 ,1 .165 ± 0 .096 and 1 .491 ± 0 .046 ,respectively （t= 4 .575 ,6 .285 and 8 .489 ,respectively ,all P〈 0 .05） .The expressions of IGFBP7 in the above three groups were 0 .497 ± 0 .021 ,1 .250 ± 0 .064 and 0 .885 ± 0 .149 ,respectively （t= 5 .161 ,30 .101 and 7 .250 , respectively ,all P 〈 0 .05 ） . Immunohistochemistry proved that the expressions of IGFBP7 in fibrosis model group and TGF-β1 vaccine group were all significantly higher than control group ;and the expressions of IGFBP3 in fibrosis model group and TGF-β1 vaccine group were all significantly lower than control group .The expressions of IGFBP3 protein in control group , hepatic fibrosis model group and vaccine intervention group were 7 .508 ± 0 .357 ,5 .200 ± 0 .210 and 5 .751 ± 0 .178 ,respectively （t = 7 .622 ,6 .180 and 29 .156 , respectively ,all

关 键 词：肝硬化 胰岛素样生长因子结合蛋白质3 胰岛素样生长因子结合蛋白质7 转化生长因子β1疫苗 二甲基亚硝胺 大鼠 

分 类 号：R575.2[医药卫生—消化系统]