肝窦毛细血管化在二甲基亚硝胺大鼠肝纤维化门静脉高压形成中的作用  

The role of hepatic sinusoid capillarization during the formation of portal hypertention in fibrotic rats induced by dimethylnitrosamine

作　　者：陆雄[1] 刘平[2] 徐光福[3] 刘成海[1] 李风华[1] 刘成[1] 

机构地区：[1]上海中医药大学病理教研室,200032 [2]上海中医药大学肝病研究所附属曙光医院肝硬化科 [3]北京中医药大学

出　　处：《中华肝脏病杂志》2003年第10期595-598,共4页Chinese Journal of Hepatology

基　　金：国家杰出青年科学基金(39825128)

摘　　要：目的 研究肝窦毛细血管化在二甲基亚硝胺(DMN)大鼠肝纤维化门静脉高压形成中的作用。方法经4周12次腹腔注射DMN制备火鼠肝纤维化模型,应用电镜技术、免疫组织化学方法结合大鼠门静脉压力测定,24周动态分析肝纤维化形成过程中肝窦毛细血管化与门静脉压力变化的相关性。结果 大鼠门静脉压力随着造模的进行不断升高,造模4周时达(1.10 ±0.18)kPa,明显高于对照组(0.52±0.04)kPa(t=6.41.P<0.0 1)。造模停止后,大鼠门静脉压力逐渐恢复正常。其动态变化与电镜下肝窦毛细血管化的变化规律一致;与反映肝窦内皮表型改变的第Ⅷ因子相关抗原的动态变化成正相关(r=0.833,P<0.01);与反映肝窦内皮下基底膜形成的层黏连蛋白的动态变化成正相关(r=0.953,P<0.01);与反映肝窦壁星状细胞活化收缩的α-平滑肌肌动蛋白的动态变化成正相关(r=0.919,P<0.01)。结论 肝窦毛细血管化是DMN肝纤维化模型门静脉高压产生的主要原因。Objective To study the role of hepatic sinusoid capillarization during the formation of portal hypertention in fibrotic rats induced by dimethylnitrosamine (DMN). Methods Hepatic fibrotic rats were induced by administration of DMN intraperitoneally three times a week for 4 weeks. The rats were harvested on day 2 and weeks 1, 2, 3, 4, 5, 6, 8, 12 and 24. The formation of liver fibrosis and hepatic sinusoid capillarization were observed by morphologic methods. Pressure of portal vein (Ppv) was directed measured with intubtion tube method by mesentry anterior vein. Results The Ppv was getting higher and higher with the administration of DMN. After four weeks, the Ppv was higher than that of control (1.10 kPa±0.18 kPa vs 0.52 kPa±0.04 kPa, t = 6.41, P < 0.01). The dynamic change of hepatic sinusoid capillarization was in accordance with that of Ppv, which normalized gradually after the DMN was stopped. Significant positive correlation existed between the dynamic change of Ppv and the expression of vWF, laminin and a -SMA in sinus (r = 0.833, P < 0.01; r = 0.953, P < 0.01; r = 0.919, P < 0.01). Conclusion Hepatic sinusoid capillarization is the vital cause for portal hypertention in fibrotic rats induced by DMN.

关 键 词：肝窦毛细血管化 二甲基亚硝胺 大鼠 肝纤维化 门静脉高压 

分 类 号：R575.2[医药卫生—消化系统]