结缔组织生长因子在血吸虫病肝纤维化鼠肝窦内皮细胞中的表达及意义

目的:动态观察结缔组织生长因子(CTGF)蛋白在血吸虫病肝纤维化鼠肝窦内皮细胞表达水平的时相变化,探讨其与肝窦内皮细胞下基底膜形成的关系。方法:采用腹部敷贴法建立血吸虫病肝纤维化模型,HE、Masson染色和透射电镜观察其病理变化;免疫组化技术检测CTGF、Ⅳ型胶原(ColⅣ)和层粘连蛋白(LN)在小鼠肝脏组织中的表达和分布;并应用彩色图像分析仪进行定量分析。结果:与正常对照组比较,模型组鼠肝窦内皮细胞表达CTGF蛋白阳性或强阳性,肝窦壁LN、ColⅣ表达水平增高,且随着肝纤维化的发展,CTGF和LN、ColⅣ表达逐渐增强,肝窦内皮下基底膜逐渐增厚。图像定量分析两组平均吸光度值、平均灰度值和阳性面积比具有统计学差异;CTGF蛋白与LN、ColⅣ水平呈正相关。结论:血吸虫病肝纤维化时小鼠肝窦内皮细胞通过CTGF蛋白表达上调,调控细胞外基质产生,导致ColⅣ、LN分泌增加,参与肝窦内皮下基底膜形成,从而引起肝内微循环障碍。

Expression of Connective Tissue Growth Factor in Sinusoidal Endothelial Cells of Schistosomal Hepatic Fibrosis Mouse

Objective: To observe the expression of connective tissue growth factor(CTGF)in sinusoidal endothelial cells of schistosomal hepatic fibrosis mouse, and to explore the possible association of CTGF with the formation of basal membrane under hepatic sinusoidal endothelial cell.Method: The liver fibrosis model was established by abdominal infection with schistosomal cercaria in 40 mice,and the control group consisted of 40 mice.The dynamic change of liver fibrosis was observed at different time points(45 d、60 d、90 d、120 d)by optic and electron microscope.The expression and distribution of CTGF、collagen type Ⅳ(ColⅣ)and laminin(LN)were detected by immunohistochemistry method. Results: In schistosomal hepatic fibrosis mice,CTGF protein staining of sinusoidal endothelial cell was positive or strong positive at 120 d and there were increases of LN、ColⅣ protein in hepatic sinusoidal walls(P<0.05).The expression of CTGF protein was positively correlated to the level of LN、ColⅣ(r=0.7512、0.6417 P<0.01). Conclusion: Hepatic sinusoidal endothelial cell of schistosomal hepatic fibrosis mice enhance the formation of extracellular matrix by upregulating expression of CTGF which induced the increase of LN、ColⅣ expression,facilitating the formation of basal membrane under hepatic sinusoidal endothelial cell.