硬脑膜血管内皮细胞生长因子表达及增殖活性与慢性颅内静脉压增高状态

Expression of vascular endothelial growth factor and proliferating activity of endothelial cells in dural vessels under chronic intracranial venous hypertension

目的:探讨慢性颅内静脉压增高状态下硬脑膜血管内皮细胞血管内皮细胞生长因子(vascularendothelialgrowthfactor,VEGF)表达及增殖活性的变化。方法:实验在解放军沈阳军区总医院动物实验中心完成。选择Wistar雄性大鼠65只,造模成功24只,随机分为实验组12只,对照组12只,右侧颈总动脉和颈外静脉端-端吻合,同时结扎上矢状窦,建立慢性颅内静脉压增高的动物模型;90d后采用免疫组化方法检测硬脑膜血管内皮细胞中VEGF及增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)的表达情况。结果:对照组的硬脑膜血管中VEGF仅呈微弱表达,其吸光度值(A)为2.12±0.59,实验组硬脑膜中血管内皮细胞VEGF表达A值为8.66±1.75,两者相比实验组微血管生成数量显著增高(P<0.05);微血管密度(×200倍计数)对照组为(3.04±0.31)/视野,实验组为(11.70±2.36)/视野,两者相比实验组微血管生成密度显著增高(P<0.05)。对照组的硬脑膜血管中PCNA仅呈微弱表达,其A值为1.12±0.19,实验组硬脑膜血管内皮细胞中PCNA表达A值为6.46±1.02。两者相比实验组血管内皮细胞增殖活性显著增高(P<0.05)。结论:慢性静脉压增高状态下硬脑膜血管内皮细胞VEGF表达升高,PCNA增殖活跃,可能与血管生成及动静脉畸形的发生发展有关。

AIM:To study the expression of vascular endothelial growth factor(VEGF) and proliferating activity of endothelial cells in dural vessels under chronic venous hypertension in rat model. METHODS:The experiment was completed in the Center for Experimental Animals,General Hospital of Shenyang Military Command.Twenty four of the selected 65 male Wistar rats were modeled successfully and divided into experimental group(n=12) and control group(n=12).The rat model of intracranial venous hypertesion was developed by creating an end to end anastomosis of right common carotid artery and external jugular vein as well as a superior sagittal sinus ligation.After 90 days,the expression of VEGF and proliferating cell nuclear antigen(PCNA) in endothelial cells of dural vessels were observed with immunohistochemistry. RESULTS:The absorbance(A) of VEGF in the control group was mildly expressed(2.12±0.59),while in the experimental group it was 8.66 ±1.75.The number of microvascularization was significantly increased in the experimental group,as compared with that in the control group(P< 0.05). The microvessel density(MVD,×200 times counting) was(3.04±0.31) per sight in the control group and 11.70±2.36 per sight in the experimental group,so the MVD was significantly increased in the experimental group,as compared with that in the control group(P< 0.05).The A value of PCNA in the control group was slightly expressed(1.12±0.19),but it was 6.46 ±1.02 in the experimental group.The proliferating activity of dural vascular endothelial cells was significantly promoted in the experimental group,as compared with that in the control group(P< 0.05). CONCLUSION:The expression of VEGF and proliferating activity of dural vascular endothelial cells were increased under chronic venous hypertension,which may play an important role in the angiogenesis and development of dural arteriovenous malformations.