缺血预适应对局灶性脑缺血再灌注大鼠海马 CA1 区低氧诱导因子-1α、 血管内皮生长因子表达的影响#br#

目的 观察缺血预适应后局灶性脑缺血再灌注大鼠缺血侧海马 CA1 区低氧诱导因子（HIF） -1α、 血管内皮生长因子（VEGF）表达的变化， 探讨缺血预适应的脑保护机制。方法 雄性 SD 大鼠随机分为 3 组： 假手术（SO）组、 脑缺血（MCAO）组和缺血预适应（BIP）组， 后两组按缺血后再灌注时间不同分为再灌注 2、 6、 12、 24、 48、 72 h 6 个亚组。制备大鼠局灶性脑缺血预适应模型， 采用免疫组织化学法与 Western blot 法观察脑缺血后再灌注各个时间点海马 CA1 区 HIF-1α和 VEGF 的表达变化。结果 SO 组未见神经功能缺损症状， 与 MCAO 组相比， BIP 组再灌注各时间点神经功能缺损评分低 （P＜0.05）。MCAO 组、 BIP 组 HIF-1α、 VEGF 阳性细胞及蛋白表达均于再灌注 2 h 开始增多， 6～12 h 表达递增， 24 h 表达至高峰， 随后表达减少， 72 h 表达仍高于 SO 组。两组各时间点 HIF-1α和 VEGF阳性细胞及蛋白表达均高于 SO 组 （P＜0.05）。除再灌注 2 h、 6 h MCAO 组与 BIP 组 HIF-1α的阳性细胞表达差异无统计学意义外， 2 组各时间点 VEGF 阳性细胞表达、 HIF-1α、 VEGF 蛋白表达均是 BIP 组高于 MCAO 组（P＜0.05）。结论 脑缺血预适应可能通过上调 HIF-1α、 VEGF 的表达， 发挥脑保护作用。

Effects of focal ischemic preconditioning on the expression of HIF-1α and VEGF in ischemia hippocampus CA1 region after focal cerebral ischemia/reperfusion in rats#br#

Objective To observe the changes of ischemic preconditioning on the expression of hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in ischemia hippocampus CA1 region after focal cerebral ischemia/reperfusion (I/R) in rats, and the mechanisms of brain protection from brain ischemia preconditioning (BIP) thereof. Methods The male SD rats were randomly divided into three groups： sham operation (SO) group， middle cerebral artery occlusion (MCAO) group and brain ischemia preconditioning (BIP) group. The MCAO group and BIP group were further divided into six subgroups according to perfusion time after I/R including 2 h, 6 h, 12 h, 24 h, 48 h and 72 h. The ischemia preconditioning model rats were established. Immunohistochemistry and Western blot assay were used to observe the expressions of HIF-1α and VEGF in ischemia hippocampal CA1 region. Results Neurological function deficit was not observed in SO group. Compared with MCAO group, there was a lower neurological function deficit score in BIP group. In MCAO group and BIP group, the expressions of HIF-1α and VEGF positive cells and protein increased at 2 h after I/R, then gradually increased from 6 h to12 h and reached the maximum level at 24 h, then gradually decreased. The levels were still higher at 72 h than those of SO group. The number of HIF-1α and VEGF positive cells and protein were significantly increased in MCAO group and BIP group than that of SO group (P < 0.05). The number of HIF-1α positive cells was higher in BIP group than that in MCAO group except 2 h and 6 h reperfusion groups. The expression of VEGF positive cells, HIF-1α and VEGF protein were significantly higher in BIP group than those in MCAO group at different time points (P < 0.05). Conclusion Ischemic preconditioning plays a protective role in brain, which may be related to up-regulation of HIF-1α and VEGF.