外源性拟载脂蛋白E肽对脑血管痉挛后血管内皮生长因子介导的脑动脉内皮细胞凋亡的影响

Effect of apoE-mimetic peptide on expression of VEGF and apoptosis of endotheliocyte in vasospastic intracranial arteries

目的：探讨外源性拟载脂蛋白E（apoE）肽对脑动脉痉挛后内皮细胞凋亡的调节作用及对血管内皮生长因子（VEGF）表达的影响。方法：采用非开颅血管内穿线法制备小鼠蛛网膜下腔出血模型并给予apoE-1410肽，术后行神经功能评分并检测大脑中动脉直径变化，应用原位杂交法、免疫印迹法检测各组右侧大脑动脉VEGF表达，TUNEL法检测大脑中动脉内皮细胞凋亡。结果：出血组小鼠神经功能评分均降低，大脑中动脉直径减小，VEGFmRNA及VEGF蛋白显著升高，TUNEL显色阳性。治疗组小鼠神经功能评分及大脑中动脉管径增加，VEGF表达降低，内皮细胞凋亡数目减少。VEGFmRNA表达与TUNEL呈正相关。结论：蛛网膜下腔出血后痉挛脑动脉内皮细胞凋亡与VEGF高表达有关；拟apoE-1410肽对脑血管痉挛具有一定的治疗作用，其机制之一可能是通过抑制VEGF活化，减少大脑中动脉内皮细胞凋亡。

Objective： To approach the role of apoE-mimetic peptide in regulation of apoptosis of endotheliocyte in vasospastic intracranial arteries, and its influence on vascular endothelial growth factor （VEGF）. Methods： We made a stable and reliable mouse subarachnoid hemorrhage （SAH） model by endovascular perforation without opening cranium, and then examined neurological score, SAH grading scale in definite time. HE staining were performed to observe representative histological structural changes of the middle cerebral arteries （MCA）, the gene expression of VEGF mRNA at 72 h after SAH was as- sayed by in situ hybridization, Western blot was used to examine the VEGF expression, and the number of apoptotic cells were determined by TUNEL. Results： The neurological function scores in SAH mice were significantly lower. SAH pro- duced severe acute vasospasm in the MCA. The diameters of MCA in SAH mice were smaller than those in the control mice. The result of TUNEL staining was positive, the gene expression of VEGF mRNA and VEGF expression was significantly increased. The neurological function scores of SAH＋apoE group were higher than those of SAH group. TUNEL revealed that the apoptosis level of endothelial cells in the SAH group treated with apoE-1410 was significantly lower than that in the SAH group, and vasospasm were relieved. The quantification of VEGF expression was positively correlated with the expres- sions of TUNEL. Conclusion： VEGF contributes to early brain injury after SAH by enhancing the activation of the VEGF; apoE-1410 reduces early brain injury after SAH and apoptotic of cerebral arteries endothelial cells by inhibiting the activation of the VEGF expression.