DDR2与MMP2在酒精性肝病肝窦毛细血管化中的协同表达  

Coordinated expression of discoidin domain receptor 2 and matrix metalloproteinase 2 in alcoholic liver disease with hepatic sinusoidal cappillatization

作　　者：阎明[1] 刘慧敏[1] 张喜红[2] 张玉泉 罗争[1] 

机构地区：[1]山东大学医学院附属齐鲁医院消化科,山东济南250012 [2]聊城市人民医院急诊科,山东聊城252004 [3]龙口市人民医院内二科,山东烟台265701

出　　处：《中国病理生理杂志》2010年第8期1515-1520,共6页Chinese Journal of Pathophysiology

基　　金：山东省科技攻关计划资助项目(No.2007GG30002002)

摘　　要：目的:探讨盘状区域受体2(DDR2)与基质金属蛋白酶(MMP2)在酒精性肝纤维化大鼠肝窦毛细血管化病理进程中的表达及可能发挥的作用。方法:橄榄油拌平衡饲料喂养大鼠的基础上给予60%(V/V)白酒胃内灌注制备酒精性肝纤维化模型,分别于4周、8周、12周和16周末观察肝组织网状纤维染色、免疫组化染色(Ⅰ、Ⅳ型胶原及层黏连蛋白),荧光定量-PCR和Western blotting检测肝组织DDR2及MMP2基因和蛋白表达并与肝窦毛细血管化各项评价指标进行相关性分析。结果:大鼠白酒灌胃4周出现肝脏脂肪变性,随灌胃时间延长逐渐加重为肝脏坏死、炎症及纤维化。酒精性肝病模型组大鼠DDR2 mRNA和蛋白表达量显著高于对照组,且随造模时间延长表达增加(P<0.01)。MMP2 mRNA和蛋白表达自造模4周开始升高,于12周达峰值,造模16周下降,各模型组MMP2 mRNA和蛋白表达较正常对照组明显升高(P<0.05)。相关性分析显示DDR2与MMP2、网状纤维、Ⅰ、Ⅳ型胶原及层黏连蛋白表达均呈显著正相关。结论:在酒精性肝病肝窦毛细血管化病程中DDR2表达呈时间依赖性,其可能通过效应蛋白MMP2在肝窦毛细血管化的发生和进展中发挥重要作用。AIM： To observe the expression of discoidin domain receptor 2（DDR2） and matrix metalloproteinase 2（MMP2） in the rat model of alcoholic liver fibrosis（ALF） with hepatic sinusoidal cappillatization and to investigate the possible effect of DDR2 on the cappillatization of the sinusoids.METHODS： The ALF rat model was established by alcoholic intragastric administration plus with olive oil diet.The liver samples were harvested at the end of 4th,8th,12th and 16th week respectively to observe the development of hepatic sinusoidal cappillatization by reticular fiber straining and immunohistochemical staining of collagen type I,Ⅳ and laminin（LN）.The expression of DDR2 and MMP2 at mRNA and protein levels was also detected by RT-PCR and Western blotting respectively to make a dependability analysis with the index of hepatic sinusoidal cappillatization.RESULTS： The liver fatty degeneration was observed at the end of 4th week of alcoholic feeding,then aggravated to inflammation and fibrosis as the process of modeling extended.Compared to control group,the mRNA and protein levels of DDR2 in the liver increased markedly in ALF model groups,which also raised gradually as the process of modeling went on（P0.01）.The mRNA and protein levels of MMP2 increased gradually in ALF groups following the aggravation of fibrosis,in which the maximum was observed in 12th week group（P0.05）.The expression of DDR2 had an obviously positive correlation with the expression of MMP2,reticular fibers,collagen type I,Ⅳ and LN.CONCLUSION： DDR2 may participate in hepatic sinusoidal capillarization through the interaction with MMP2.

关 键 词：肝硬化 酒精性 肝窦毛细血管化 受体 盘状区域 基质金属蛋白酶2 

分 类 号：R575.2[医药卫生—消化系统]