肝星状细胞活化在大鼠肝硬化门脉高压形成中的作用  

Role of hepatic stellate cells activation in development of portal hypertention of dimethylnitrosamine-induced liver cirrhosis in rats

作　　者：王宪波[1] 刘平[2] 唐志鹏[2] 陆雄[2] 顾宏图[2] 

机构地区：[1]上海中医药大学附属岳阳中西医结合医院消化科,上海200437 [2]上海中医药大学肝病研究所附属曙光医院肝硬化科,上海201203

出　　处：《中国中西医结合消化杂志》2005年第4期211-214,共4页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：国家杰出青年科学基金资助项目(39825128)

摘　　要：[目的]探讨肝星状细胞(HSC)活化在大鼠肝硬化门脉高压形成中的作用。[方法]采用二甲基亚硝胺(DMN)4周12次腹腔注射制作大鼠肝硬化模型,分别于造模后1d、2d、3d、1周、2周、4周、6周、8周作为动态观察时相点,免疫组化染色观察肝组织α平滑肌肌动蛋白(αSMA)、Ⅳ型胶原(ColⅣ)、层黏连蛋白(LN)表达,电镜观察肝组织超微结构,肠系膜前静脉分支插管法测门脉压力(Ppv)。[结果]造模2、3d后肝窦壁αSMA染色逐渐增强,4周时阳性表达最为明显;模型大鼠肝窦壁ColⅣ阳性染色呈现先弱后强,LN的沉积随造模时间的延长而进行性增加,4周时表达最为明显,电镜下可见肝窦内皮失窗孔和基底膜形成;DMN大鼠HSC中αSMA表达量与Ppv高低呈显著正相关(P<0.05)。[结论]活化的HSC通过分泌大量的ColⅣ和LN形成肝窦内皮下基底膜以及因表达αSMA而收缩力增强,是肝硬化肝窦阻力增加和门脉高压形成的重要病理细胞学基础。[Objective]To study the role of hepatic stellate cells （HSC） activation in the development of portal hypertention of dimethylnitrosamine （DMN）-induced liver cirrhosis in rats.[Methods] Rat liver cirrhosis model was established by peritoneal injection of DMN （at a dose of 10 mg·kg-1 , 3 times a week, for 4 weeks）. Dynamic changes of liver fibrosis were observed at different time points （1 d, 2 d, 3 d, 1 w, 2 w, 4 w, 6 w and 8 w）. Pressure of portal vein （Ppv）was directly measured with intubatton method by mesentery anterior vein. Expression of alphasmooth muscle actin （α-SMA）, type IV collagen （Col IV） and laminin （LN） was examined by immunohistochemistry. I.iver ultrastructure was observed by electron microscope. I-Results] Positive expression of α-SMA in the normal liver sinusoidal walls increased 2d and 3d after DMN injection, and the strongest positive staining displayed in the 4w model rats. The change of positive staining of Col IV from weak to strong was observed in the liver sinusoidal walls of the fibrosis model. Positive expressions of LN, and the strongest positive staining displayed in the 4w model rats. Meanwhile, loss ot tenestrate in the HSC and formation of basal membrane increased.There was remarkable positive correlation between the expressions of α-SMA and Ppv in the DMN-induced rat fibrosis （ P〈0.05）. [Conclusion]The activated HSC are the important pathological cell basis of liver resistance increase and development of portal hypertention by producing plenty of Col Ⅳ and LN that contributes to the formation of basal membrane and expressing α-SMA that increases contractility.

关 键 词：肝硬化 肝星状细胞 大鼠 门脉高血压 

分 类 号：R575.2[医药卫生—消化系统] R657.3[医药卫生—内科学]