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目的:探讨血管内皮生长因子(VEGF)在脑缺血耐受中的作用及其与血管形成的关系。方法:Wistar大鼠线栓法阻塞大脑中动脉建立局灶性缺血预处理模型,并进行神经功能评分。随机分为假手术(对照组)、非缺血预处理(NIP)组和缺血预处理(IP)组,NIP和IP组再根据不同时间窗随机分成5个亚组。分别在缺血预处理后1、3、7、14和21 d进行再次缺血2 h再灌注22 h,然后取脑检测:TTC染色测定脑梗死体积,计数微血管密度,免疫组化检测CD34和VEGF蛋白表达,原位杂交法检测VEGF mRNA表达。结果:①组间比较:IP 1、3和7 d亚组脑梗死体积较NIP组明显减小(P<0.01),其神经行为缺损评分也明显降低(P<0.05);IP 3和7 d亚组脑微血管密度明显增高(P<0.05);IP 1、3和7 d亚组VEGF蛋白及mRNA表达明显增高(P<0.05,P<0.01)。②组内比较:IP 7 d亚组微血管在缺血灶周边区分布最为密集,脑微血管密度明显高于同组内其他亚组(P<0.05);IP 3和7 d亚组VEGF蛋白表达明显增高,VEGF mRNA表达在IP 1 d即开始升高,高峰出现在IP 3 d,持续至7 d。结论:缺血预处理诱导了脑缺血耐受,缺血预处理诱导的VEGF表达增加以及血管形成在脑缺血耐受中发挥重要作用。
Objective: To investigate the role of vascular endothelial growth factor (VEGF) in cerebral ischemic tolerance and its relationship with angiogenesis. Methods: The focal ischemic preconditioning model was established by occlusion of the middle cerebral artery (MCAO) by Wistar rats and the neurological function was evaluated. The rats were randomly divided into sham operation (control group), non-ischemic preconditioning (NIP) and ischemic preconditioning (IP) groups. NIP and IP groups were randomly divided into 5 subgroups according to different time windows. The ischemic preconditioning was performed again at 2 h, reperfusion for 2 h at 1, 3, 7, 14 and 21 days after ischemia preconditioning, respectively. Then the brain was taken for measurement of cerebral infarction volume by TTC staining and the microvessel density was counted. CD34 VEGF protein expression, in situ hybridization VEGF mRNA expression. Results: ①Comparison between groups: The volume of cerebral infarction in IP 1,3 and 7 d subgroups was significantly reduced (P <0.01) and the neurobehavioral deficit score was also significantly decreased (P <0.05); IP 3 and 7 d The brain microvessel density was significantly increased in subgroups (P <0.05). The expression of VEGF protein and mRNA in subgroups of IP 1,3 and 7 d were significantly increased (P <0.05, P <0.01). ② In-group comparison: The distribution of microvessels in the IP 7 d subgroup was the most intensive in the peripheral zone of ischemic foci, and the density of cerebral microvessels was significantly higher than other subgroups in the same group (P <0.05). The expression of VEGF protein in IP 3 and 7 d subgroups was significantly The expression of VEGF mRNA began to increase on the 1st day after IP, peaked at IP 3 d for 7 days. CONCLUSION: Ischemic preconditioning induces cerebral ischemic tolerance, increases in VEGF expression induced by ischemic preconditioning, and angiogenesis play an important role in cerebral ischemic tolerance.