目的:探讨肝窦内皮细胞(SECs)损伤和表型改变与大鼠肝硬化门脉高压的关系。方法:采用二甲基亚硝胺(DMN)4周12次腹腔注射复制大鼠肝硬化模型,分别于造模后1d、2d、3d、1周、2周、4周、6周、8周作动态观察;肠系膜前静脉分支插管法测门脉压力(Ppv);透射电镜观察肝组织超微结构;免疫组化观察肝窦壁CD44和Ⅷ因子相关抗原(vWF)表达;Northernblot检测肝组织内皮素-1(ET-1)mRNA和内皮型一氧化氮合酶(eNOS)mRNA表达;Westernblot检测肝组织eNOS表达;放射免疫法测定血清透明质酸(HA)和肝组织ET-1含量。结果:DMN造模1d后CD44染色明显弱于正常对照组(P<0.05),SECs窗孔减少,血清HA含量显著高于正常对照组(P<0.05);DMN造模2d后vWF阳性染色明显强于正常对照组(P<0.05);DMN大鼠的Ppv与肝窦壁vWF表达量和血清HA含量呈显著正相关(P<0.05);造模2d和3d时ET-1mRNA表达强于正常对照组,ET-1含量轻度高于正常对照组;造模1d、2d和3d时eNOSmRNA表达强于正常对照组,而eNOS一直呈低水平状态。结论:SECs损伤和表型改变是DMN大鼠肝硬化门脉高压形成的病理基础之一;ET-1和NO产生的平衡失调,使肝内血流阻力增加,在门脉高压形成过程中起重要作用。 Objective: To investigate the relationship between changes of hepatic sinusoidal endothelial cells (SECs) and phenotypic changes in cirrhotic patients with portal hypertension. Methods: Twelve intraperitoneal injections of dimethylnitrosamine (DMN) were used to replicate rat models of liver cirrhosis. The rats were sacrificed at 1, 2, 3d, 1, 2, 4, 6 and 8 weeks after modeling The portal vein pressure (Ppv) was measured by the branch of the mesenteric vein. The ultrastructure of hepatic tissue was observed by transmission electron microscope. The expression of CD44 and vWF in the hepatic sinusoidal wall was observed by immunohistochemistry. (ET-1) mRNA and endothelial nitric oxide synthase (eNOS) mRNA were detected by Western blot. The expression of eNOS in liver tissue was detected by Western blot. The levels of serum hyaluronic acid (HA) and ET-1 in liver tissue were determined by radioimmunoassay. Results: After 1 day of DMN, CD44 staining was significantly weaker than that of normal control group (P <0.05), while the number of SECs was decreased and serum HA level was significantly higher than that of normal control group (P <0.05). Ppv was positively correlated with vWF expression in sinusoidal wall and serum HA level in DMN rats (P <0.05), while expression of ET-1 mRNA in DMN rats was stronger than normal rats at 2d and 3d The content of ET-1 in the control group was slightly higher than that in the normal control group. The expression of eNOS mRNA in the control group was higher than that of the control group at 1d, 2d and 3d, while eNOS was always low. Conclusion: The changes of SECs injury and phenotype are one of the pathological basis of portal hypertension in cirrhotic rats with DMN. The imbalance of ET-1 and NO production increases the intrahepatic flow resistance and plays an important role in the formation of portal hypertension Important role.