局部脑缺血后血管活性肠肽促进血管再生

Vasoactive intestinal peptide enhances angiogenesis after focal cerebral ischemia

目的研究局部脑缺血后血管活性肠肽(VIP)对血管再生的影响。方法通过闭塞成年SD大鼠大脑中动脉(MCAO)120min诱导建立局部脑缺血,缺血再灌注后大鼠侧脑室内注射VIP。采用免疫组织化学染色观测缺血边缘区血管再生、VEGF及其受体的表达;Western blotting分析脑内VEGF蛋白含量。结果免疫组织化学染色显示VIP组大鼠脑缺血区周围BrdU免疫反应内皮细胞较对照组明显增加(P<0.05);VIP组大鼠脑缺血边缘区VEGF免疫反应细胞以及flt-1和flk-1免疫反应内皮细胞较对照组均显著增多(P<0.01);免疫印迹分析表明VIP组大鼠缺血侧脑组织VEGF蛋白水平较对照组大鼠明显上调(P<0.05)。结论VIP可以促进缺血脑的血管再生;上调的VEGF及其受体可能介导了VIP促血管再生作用。

Objective To investigate the effect of vasoactive intestinal peptide （VIP） on angiogenesis after focal cerebral ischemia. Methods Focal cerebral ischemia was induced by middle cerebral artery occlusion （MCAO） for 120 min in adult SD rats with intracerebroventricular VIP administration at the beginning of reperfusion. Immunohistochemistry was performed to assay BrdU immunoreactive endothelial cells, expressions of VEGF, fit-1 and fik-1 in the ischemic zone, and the protein expressions of vascular endothelial growth factor （VEGF） in the brain was measured using Western blotting. Results Immunohistochemical staining revealed significantly increased BrdU immunoreactive endothelial cells on the margins of the ischemic lesion in rats treated with VIP as compared with that in the control rats （P〈0.05）. VIP significantly increased the number of VEGF immunoreactive cells and fit-l- and ilk-l-positive endothelial cells in comparison with the control group （P〈0.01）. Western blotting showed that VIP treatment resulted in significantly increased VEGF protein level in the ipsilateral hemisphere （P〈0.05）. Conclusion VIP enhances angiogenesis in the ischemic brain by increasing the expressions of VEGF in the brain tissue and its receptors fit-1 and flk-1 in the endothelial cells.