缺血预适应对局灶性脑缺血再灌注大鼠皮质区低氧诱导因子-1α和血管内皮生长因子表达的影响

Cerebral ischemic preconditioning increases the expressions of HIF-1α and VEGF in the cortex area of rats with focal cerebral ischemia / reperfusion injury

目的缺血预适应诱导脑缺血耐受已成为缺血性脑血管疾病的研究热点,但其具体机制尚未阐明。文中通过观察缺血预适应后局灶性脑缺血再灌注大鼠梗死灶周边皮质区低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的变化,探讨缺血预适应的脑保护机制。方法将130只雄性SD大鼠随机分为假手术组、脑缺血组和预适应组,脑缺血组和预适应组按缺血后再灌注时间不同分为再灌注2、6、12、24、48和72 h 6个亚组,假手术组10只大鼠,其余每个时间点各10只大鼠。采用改良线栓法制备大鼠局灶性脑缺血预适应模型,通过免疫组织化学法与Western blot法观察脑缺血后再灌注各个时间点HIF-1α和VEGF的表达变化。结果脑缺血组、预适应组于再灌注2 h HIF-1α和VEGF阳性细胞及蛋白表达有所增加,24 h表达至各时间点最高水平,随后表达逐渐减少,72 h表达仍明显高于假手术组(P<0.05)。预适应组各时间点HIF-1α、VEGF的阳性细胞及蛋白表达均高于脑缺血组,差异有统计学意义(P<0.05);脑缺血组、预适应组组内各相邻时间点比较,差异有统计学意义(P<0.05)。假手术组HIF-1α和VEGF阳性细胞及蛋白仅少量表达。结论脑缺血再灌注损伤能够诱导HIF-1α、VEGF的表达,脑缺血预适应能够进一步上调两者表达。

Objective Cerebral ischemic tolerance induced by cerebral ischemic preconditioning has become a hotspot in the researches of ischemic cerebrovascular disease, and its specific mechanism remains to be clarified.This study was to explore the brain protection mechanisms of cerebral ischemic preconditioning by observing the expressions of HIF-1αand VEGF in the cortex area sur-rounding the infarct locus in rats with focal cerebral ischemia /reperfusion （ I/R） after cerebral ischemic preconditioning. Methods A total of 130 male SD rats were randomly divided into three groups：sham operation, middle cerebral artery occlusion, and cerebral is-chemic preconditioning, the animals in the latter two groups subjected to 2, 6, 12, 24, 48 and 72 h of I/R.The expressions of HIF-1α and VEGF at different time points were detected by immunohistochemistry and Western blot. Results In the middle cerebral artery occlusion group, the expressions of HIF-1αand VEGF positive cells and proteins increased at 2 h after I/R, reached the peak at 24 h, and then gradually decreased to and at 72 h, but still higher than in the sham operation group （P〈0.05）.The expressions of HIF-1αand VEGF positive cells were significantly higher in the cerebral ischemic preconditioning than in the middle cerebral artery occlusion group （all P〈0.05）, so were the expressions of HIF-1αand VEGF positive proteins in the former group than in the latter （all P〈0.05）.The sham operation group showed only a little in-crease in the expressions of HIF-1αand VEGF positive cells and proteins. Conclusion Cerebral ischemia reperfusion injury induces the expressions of HIF-1αand VEGF, which can be further upregulated by brain ischemic preconditioning.