小凹蛋白-1与内皮型一氧化氮合成酶活性变化在大鼠门静脉高压形成中的作用  

The roles of caveolin-1 and endothelial nitric oxide synthase in the development of portal hypertension in rats with liver cirrhosis

作　　者：徐波[1] 朱光辉[1] 翁杰锋[1] 蔡文松[1] 夏金堂[1] 李书华[2] 

机构地区：[1]广州医学院附属广州市第一人民医院普外科,510180 [2]广州医学院病理教研室

出　　处：《中华肝脏病杂志》2008年第3期184-187,共4页Chinese Journal of Hepatology

基　　金：广州市医药卫生科技项目（2005-YB-032）

摘　　要：目的探讨肝硬化发生发展过程中小凹蛋白-1的动态变化及与其肝纤维化程度、门静脉压力的关系，探讨小凹蛋白-1对内皮型一氧化氮合成酶（eNOS）作用的可能调控机制。方法构建二甲基亚硝胺致肝硬化大鼠模型，分别在造模后的1、2、3、4、6周，病理组织学观察肝纤维化程度及测定门静脉压力（PVP），放射强度测定法检测肝硬化组织中eNOS活性，免疫沉淀与Western blot检测小凹蛋白-1和eNOS蛋白变化及其相互作用。结果造模过程中肝纤维化程度逐渐加重，至第4周已形成典型的肝硬化，其后逐渐减轻；免疫沉淀与Westernblot实验结果表明eNOS和小凹蛋白-1可免疫共沉淀，且小凹蛋白-1与eNOS的结合可随造模时间延长而增加；小凹蛋白-1表达与肝纤维化程度、PVP呈显著正相关（r=0．967，P〈0．01；r=0．922，P〈0．01）；NOS与肝纤维化程度、PVP呈显著负相关（r=-0．973，JP〈0．01；r=-0．947，P〈0．01）。结论小凹蛋白01作为eNOS的一个负调控因子，参与肝硬化门静咏高压的形成。Objectives To study the relationship between the dynamic changes ofcaveolin-1 with the degrees of liver fibrosis and portal venous pressure （PVP） in the process of rat liver cirrhosis formation induced by dimethylnitrosamine （DMN）; also to investigate the mechanisms of caveolin- 1 in the regulation of endothelial nitric oxide synthase （eNOS）. Methods Liver cirrhosis was induced in rats by DMN. The degrees of liver fibrosis and PVP were measured. NOS activity was assessed by citrulline generation. Protein expressions of caveolin-1, eNOS and caveolin-l-eNOS interactions were examined by Western blot and immunoprecipitation, respectively. Resdts Four weeks after DMN administration, liver fibrosis was at its peak and then decreased gradually. Immunoprecipitation and Western blot demonstrated that there was enhanced binding of caveolin-1 with eNOS in the process of rat liver cirrhosis. An increase in caveolin-1 expression was detected but the expression of eNOS was lower in cirrhotic tissues than in normal liver tissues. Caveolin-1 protein levels were positively correlated with the degrees of liver fibrosis and the levels of PVP （r = 0.967, P 〈 0.01; r = 0.922, P 〈 0.01, respectively）, while NOS catalytic activity was negatively correlated with the degrees of liver fibrosis and levels of PVP （r = -0.973, P 〈 0.01; r = -0.947, P 〈 0.01） respectively. Conclusions Caveolin-1 upregulation is associated with the development of portal hypertension in liver cirrhosis. Over-expression of caveolin-1 in perisinusoidal cells may promote caveolin- 1-eNOS binding and reduce the activity of eNOS.

关 键 词：肝硬化 一氧化氮合成酶 高血压 门静脉 大鼠 小凹蛋白-1 

分 类 号：R285.5[医药卫生—中药学]