小凹蛋白与内皮型一氧化氮合成酶在人肝硬化组织中的表达及意义

目的检测人肝硬化组织中小凹蛋白(caveolin-1)、内皮型一氧化氮合成酶(eNOS)的细胞定位及蛋白表达水平的变化,探讨caveolin-1的表达对eNOS的影响。方法免疫组织化学染色检测30例肝硬化患者活检后肝组织和30例肝外伤、肝血管瘤患者正常肝组织中caveolin-1和eNOS的细胞定位。Western印迹检测caveolin-1和eNOS的蛋白表达水平变化。结果caveolin-1和eNOS均主要分布于肝窦内皮细胞中,caveolin-1在肝硬化组和对照组表达阳性率有差异,分别为87%和40%(P<0.05)。eNOS在肝硬化组和对照组表达阳性率有差异,分别为33%和66%(P<0.05)。caveolin-1在肝硬化组织中表达较正常肝组织中明显增强。eNOS在肝硬化组织中呈低水平表达,较正常肝组织中表达明显减少。结论肝硬化肝窦内皮细胞的损伤降低了eNOS的表达。caveolin-1的过表达促进eNOS-caveolin-1复合物的形成,加剧了门静脉高压症的发生。

Expression of caveolin-1 and endothelial nitric oxide synthase in human cirrhotic liver

Objective To detect the cytological localization and expression of caveolin-1 and endothelial nitric oxide synthase(eNOS) at protein level in cirrhotic liver,and investigate the effect of caveolin-1 on eNOS activity.Methods Immunohistochemistry was used to detect the cytological localization of caveolin-1 and eNOS in the liver specimen of 30 cirrhotic patients and 30 control patients with liver injury.Western blotting was used to detect the protein level of caveolin-1 and eNOS.Results Both caveolin-1 and eNOS were mainly localized in the hepatic sinusoidal endothelial cells,and the positive rate of caveolin-1 expression was 87% in cirrhotic group and 40% in control group(P<0.05).The positive rate of eNOS expression was 33% in cirrhotic group and 66% in control group(P<0.05).Caveolin-1 was more abundantly expressed in cirrhotic liver tissue than that in normal control liver tissue at protein level by Western blotting analysis,however eNOS was weakly expressed in cirrhotic tissue and significantly lower than that in normal control liver tissue.Conclusions In human cirrhotic liver,over-expression of caveolin-1 in perisinusoidal cells may promote the binding of caveolin-1-eNOS,leading to impair NO production and increase portal venous pressure.