层黏连蛋白及其整合素受体在肝窦毛细血管化时的协调表达

The coordinated expression of laminin and its integrin receptor in hepatic sinusoidal capillarization

目的 探讨层黏连蛋白 (LN)及其整合素受体在肝窦毛细管化时的协调表达。方法 皮下注射四氯化碳制备大鼠肝纤维化模型 ,取肝组织用扫描电镜、特殊染色等进行病理组织形态学观察 ;层黏连蛋白及其整合素受体α6免疫组化检测及α6斑点免疫印迹研究。结果 动态观察了肝纤维化的特征性病理变化 :肝窦毛细血管化 ,即窗孔消失、基底膜形成及表型改变 ;LN在肝纤维化各期窦周阳性着色面积分别为 0、1 92 %、6 0 2 %、9 6 8%、14 14% ,其差异有显著性 (P <0 0 0 1) ;正常时α6在肝窦内皮细胞 (SEC)上无表达 ,肝窦毛细血管化时SEC出现α6表达与LN在窦周沉积一致 ,α6在纤维化时组织中含量明显高于正常 (P <0 0 5 )。结论 LN于肝纤维化时在肝组织中不断沉积 ,并沿肝窦壁形成基底膜 ,使肝窦毛细血管化 ,且SEC出现LN整合素受体的诱导表达。

To explore the expression of laminin and its integrin receptor α 6 in sinusoidal capillaration. Methods The rat hepatic fibrosis model was established by injection carbon tetrachloride subcutaneously. Liver sections were examined by scanning electron microscopy and special staining. Then expressions of laminin and integrin α 6 subunit were observed by immunohistochemistry and dot immuno blotting. Results The pathologic character of hepatic fibrosis sinusoidal capillaration was observed. Sinusoidal capillaration is characterized by defenestration of sinusoidal endothelial cells (SEC) and basement membrane forming and phenotype transformation. By immuohistochemistry staining, The deposition of laminin surrounding sinusoids according to fibrosis stage was 0、1.92%、6.02%、9.68%、14.14% respectively, statistically different from each other ( P <0.05). In normal rat no expression of integrin α 6 were observed in SEC membranes. When capillaration integrin α 6 was detected in a continuous pattern along the sinusoidal in accordance with laminin assembly. The content of integrin α 6 in fibrotic liver tissues were significantly higher than in normal liver tissues as measured by dot immuo blotting ( P <0.05). Conclusions During fibrogenesis laminin continuously accumulate in liver tissues and form basement membrane resulting in sinusoidal capillaration, meanwhile are company with induced expression of LN binding integrin α 6 on SEC membranes. These results suggest that coordinated expression of laminin and laminin binding integrin might be important in pathogenesis of sinusoidal capillaration and hepatic fibrosis