外源性血管内皮生长因子对肝硬化大鼠肝组织血管的影响

Effect of exogenous administration of vascular endothelial growth factor on hepatic microvessel density in rats with liver cirrhosis

目的:研究外源性血管内皮生长因子对肝硬化大鼠肝脏组织内血管的影响,以检测肝硬化大鼠肝脏微循环变化.方法:25只肝硬化门静脉高压造模成功SD♂大鼠,体质量180-220g,随机分为肝硬化门静脉高压对照组(B组,n=10)和肝硬化门静脉高压实验组(C组,n=15),C组应用Alzet微渗泵从大鼠门静脉连续泵入血管内皮生长因子持续2wk,正常对照组(A组,n=10)和B组开腹后关腹作对照,2wk后对各组大鼠在光镜和电镜下进行肝组织病理学观察,用免疫组织化学方法,以Ⅷ因子相关抗原标记微血管数目,检测大鼠肝脏微血管变化.结果:光镜下观察C组肝纤维化程度较B组减轻,电镜下观察B组肝窦内皮细胞形态不规则,窗孔缺失,基底膜形成,C组病变减轻.免疫组织化学显示,在肝脏间质组织中,C组肝脏微血管数目较B组数目增加(2.04±0.61vs1.26±0.30,P<0.01),在肝脏实质组织中,C组微血管数目较B组数目减少(0.74±0.05vs1.32±0.48,P<0.01).在肝脏实质与间质组织中,B组和C组微血管数目均高于A组(1.26±0.30,2.04±0.61vs0.70±0.07;1.32±0.48,0.74±0.05vs0.28±0.08,均P<0.05).结论:外源性血管内皮生长因子能够增加肝硬化大鼠肝脏间质组织中微血管数目,并同时减少肝脏实质组织中微血管数目,能够改善肝脏的微循环情况.

AIM：To investigate the effect of portal vein administration of vascular endothelial growth factor on the density of hepatic microvessels in rats with liver cirrhosis.METHODS：Twenty-five male Sprague-Dawley rats with portal hypertension were randomly divided into two groups：treatment group（n=15） and model group（n=10）.The treatment group was given recombinant rat vascular endothelial growth factor 165（30 ng/d）via the portal vein for 2 weeks.The model group underwent only sham operation.Ten normal rats were used as normal controls.After treatment,liver histopathology was examined by light microscopy and sinusoidal ultrastructure was observed by transmission electron microscopy.The density of hepatic microvessels was detected by immunostaining of von Willebrand factor（vWF）.RESULTS：Light microscopy examination showed that hepatic fibrosis improved in the treatment group compared with the model group.Electron microscopy analysis showed decreased number of fenestrations in sinusoidal endothelial cells,basement membrane formation,and irregular hepatic sinus endothelial cells.These pathological changes were more severe in the model group than in the treatment group.Microvessel density was higher in fibrotic stroma （2.04±0.61 vs 1.26±0.30,P0.01）but lower in liver parenchyma（0.74±0.05 vs 1.32±0.48,P 0.01）in the treatment group than in the model group.However,microvessel density in both liver stroma and parenchyma was higher in the treatment and model groups than in the normal control group（1.26±0.30,2.04±0.61 vs 0.70± 0.07;1.32±0.48,0.74±0.05 vs 0.28±0.08,all P 0.05）.CONCLUSION：Exogenous administration of vascular endothelial growth factor is capable of increasing the number of microvessels in fibrotic stroma but decreasing that in liver parenchyma.