胶囊渗透压泵控释rmIGFBPrP1对小鼠肝肾组织的影响及意义  

The effect and significance of exogenous IGFBPrP1 on liver and kidney tissue in mice

作　　者：冯建文[1] 刘立新[1] 张海燕[1] 张骞骞[1] 

机构地区：[1]山西医科大学第一医院科研实验中心,太原030001

出　　处：《临床肝胆病杂志》2011年第8期827-832,836,共7页Journal of Clinical Hepatology

基　　金：国家自然科学基金(30871146);山西省回国留学人员科研资助项目(2009-44)

摘　　要：目的胶囊渗透压泵植入野生型小鼠皮下并持续恒量释放重组鼠胰岛素样生长因子结合蛋白相关蛋白1(rmIGFBPrP1),观察小鼠肝肾纤维化相关指标的表达,探讨rmIGFBPrP1对小鼠肝肾组织的影响及其可能的意义。方法将清洁级雄性C57BL/6野生型小鼠随机分为正常对照组、假手术组、模型组。采用胶囊渗透泵控释rmIGFBPrP1制备肝纤维化模型。HE染色、天狼猩红染色观察各组小鼠肝肾病理改变及胶原纤维沉积状况。免疫组织化学染色检测肝肾组织中IGFBPrP1、Smad3、p-Smad2/3、Ⅲ型胶原(CollagenⅢ)的表达和分布。原位缺口末端标记技术(TUNEL)检测肝细胞凋亡。结果与对照组和假手术组相比,模型组肝组织中胶原纤维含量增多,IGFBPrP1、Smad3、p-Smad2/3、CollagenⅢ表达增强(P<0.01)。模型组肾组织中仅IG-FBPrP1表达较对照组和假手术组有所增加,胶原纤维和其他指标表达未见差异(P>0.05)。TUNEL结果显示模型组肝细胞凋亡率增高,与正常组和假手术组相比,差异有统计学意义(P<0.01)。结论外源性IGFBPrP1可促进小鼠肝细胞凋亡和肝纤维化的形成,而对小鼠肾组织影响甚微。IGFBPrP1致小鼠脏器组织纤维化可能具有选择性。Objective To investigate the effect of exogenous recombinant mouse insulin - like growth factor binding protein related protein 1 （ rmIGFBPrP1 ） on both liver and kidney tissue in mouse, and explore the mechanism of rmIGFBPrP1 on fibrosis. Methods A total of 26 clean male wild -type C57BL/6 mice were randomly divided into normal control group, sham -operated group and model group. The rmIG-FBPrP1 which was released by capsule osmotic pump was used to make the model. HE staining and Sirius red staining were observed to investigate the pathological changes and deposition of collagen fibers in liver and kidney of mice. The expression and distribution of IGFBPrP1, Smad3, p -Smad2/3, Ⅲ collagen （Collagen Ⅲ） of liver and kidney tissues were detected by immunohistochemistry. Hepatocyte apoptosis was detected by DUTP nick end labeling （TUNEL）. Results Comparing with the control group and sham -operated group, the content of collagen fiber and the expression of IGFBPrP1, Smad3, p - Smad2/3, Collagen Ⅲ increased （P 〈 0.01 ） in the liver of model group, While only the expression of IGFBPrP1 in the kidney of model group increased than that in the control group and sham - operated group （ P 〈 0. 01 ）, there is no difference of collagen fibers content and other indicators expression in these three groups（ P 〉0.05 ）. TUNEL showed the increase in ratio of apoptotie liver cells in model group than that in normal group and sham - operated group （ P 〈 0.01 ）. Conclusion Exogenous IGFBPrP1 can promote hepatocyte apoptosis and liver fibrosis, while have little effect on the mice kidney. IGFBPrP1 may selectively induce organs and organization fibrosis in mice.

关 键 词：胰岛素样生长因子结合蛋白相关蛋白1 肝硬化 细胞凋亡 

分 类 号：R575.2[医药卫生—消化系统]