血管内皮生长因子在实验性胆汁性肝硬化形成过程中的作用

Effect of vascular endothelial growth factor in experimental biliary cirrhosis

目的探讨血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)在实验性胆汁性肝硬化形成中的作用。方法将雄性SD(Sprague-Dawley)大鼠40只随机分为肝硬化(CIR)组30只和假手术(SO)组10只,采用胆总管结扎复制大鼠胆汁性肝硬化模型,假手术组仅游离胆总管而不结扎;于术后4周处死大鼠,抽取下腔静脉血,测定肝功能;留取肝组织分别作HE染色、VG染色及VEGF免疫组化染色,并作图像半定量分析。结果CIR组肝组织学检查显示胆汁性肝硬化的典型特征,SO组无此改变;免疫组化结果表明:CIR组VEGF呈强阳性表达,主要位于肝细胞、肝窦内皮细胞、肝内血管内皮细胞;而SO组VEGF呈弱阳性表达,主要位于肝细胞、肝窦内皮细胞;CIR组VEGF平均积分光密度值(0.108±0.036)以及胶原纤维面密度值(0.304±0.131)与SO组相比(0.031±0.015,0.060±0.038)差异均具显著性(P<0.001)。结论血管内皮生长因子可能在肝硬化进程中起着一定的保护作用。

[Objective] To investigate the role of vascular endothelial growth factor（VEGF） in experimental biliary cirrhosis in rats. [Methods] Sprague-Dawley male rats were separated into two groups randomly： cirrhotic group（CIR, n=30） and sham-operated group （SO, n=10）. Cirrhotic rats were induced by common bile duct ligation while sham-operated rats weren＇t ligated it. All rats were killed after four weeks, liver function and hepatic histology were detected, immunohistochemical staining of VEGF and intrahepatic collagen was also done respectively. The semi-quantitated content of VEGF and intrahepatic collagen was detected by photograph analysis as well. [Results] The histological changes of CIR group showed typical biliary cirrhosis, while the SO group showed no changes. Immunohistochemical staining of VEGF and intrahepatic collagen in CIR group was much stronger than that in SO group. VEGF expression was mainly detected in hepatocytes, sinosoidal endothelial cell and intrahepatic vascular endothelial cell. There was a significant difference between CIR group （0.108±0.036, 0.304±0.131） and SO group （0.031±0.015, 0.060 ±0.038） in the intrahepatic content of VEGF and collagenous fibers （P 〈0.001）. [Conclusion] VEGF may play a protective role on the pathogenesis of cirrhosis.