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  

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

作　　者：张会玲[1] 李世英[1] 李峥[2] 张晋霞[1] 贺永贵[1] 刘斌[1] 

机构地区：[1]河北联合大学附属医院神经内一科,063000 [2]唐山玉田县医院神经内科

出　　处：《天津医药》2015年第11期1284-1288,共5页Tianjin Medical Journal

基　　金：河北省2013年医学科学研究重点课题计划(20130382)

摘　　要：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、72h6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Westernblot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2h开始增多，6～12h表达递增，24h表达至高峰，随后表达减少，72h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S0组（P〈0．05）。除再灌注2h、6hMCAO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。Objective To observe the changes of ischemic preconditioning on the expression of hypoxia inducible factor （HIF）-1 and vascular endothelial growth factor （VEGF） in ischemia hippocampus CA 1 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 CA 1 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.

关 键 词：缺氧缺血 脑 芳香烃受体核转位子 血管内皮生长因子类 低氧诱导因子1-α 血管内皮生长因子 

分 类 号：R743.3[医药卫生—神经病学与精神病学]