缺血预处理对局灶性脑缺血再灌注大鼠缺血侧海马CA1区低氧诱导因子－1α及存活素表达的影响

摘要

Objective To observe the effects of ischemic preconditioning on the expression of hypoxia-inducible factor-1α( HIF-1α) and survivin at ischemia bilateral hippocampal CA1 area in rats with focal cerebral ischemia reperfusion.Methods One hundred and thirty healthy male SD rats were randomly divided into sham operation group ( SO group, n =10 ) , focal cerebral ischemia reperfusion group ( MCAO group, n =60 ) and ischemia preconditioning group ( BIP group, n=60) .The MCAO group and BIP group were further divided into reperfusion 2 h, 6 h, 12 h, 24 h, 48 h and 72 h 6 subgroups, respectively, with 10 rats in each subgroup.Sutured method was used to made focal cerebral ischemia reperfusion model rats.The BIP group received ischemic preconditioning with 10 min at 24 h before cerebral ischemia.The numbers of positive cells of HIF-1αand survivin were detected by immunohistochemistry.The relative contents of protein of HIF-1αand survivin were detected by Western blot method.Results Compared with the SO group, the numbers of positive cells and the relative contents of protein of HIF-1α, survivin at ischemia bilateral hippocampal CA1 area in subgroups at each time point of MCAO group and BIP group were significantly increased ( all P<0.05 ) .Compared with the MCAO group, the numbers of positive cells and the relative contents of protein of HIF-1α, survivin at ischemia bilateral hippocampal CA1 area in subgroups at each time point of BIP group were significantly increased ( all P<0.05) .In the MCAO group and BIP group, the numbers of positive cells and the relative contents of protein of HIF-1α, survivin at ischemia bilateral hippocampal CA1 area were all arrived the peak at reperfusion 24 h moment ( all P<0.05 ) .Conclusions Ischemic preconditioning can increase the expression of HIF-1α, survivin at ischemia bilateral hippocampal CA1 area in rats with focal cerebral ischemia reperfusion.It may be related to the mechanism of cerebral ischemia tolerance.%目的：探讨缺血预处理对局灶性脑缺血再灌注大鼠缺血侧海马CA1区低氧诱导因子－1α（ HIF－1α）及存活素表达的影响。方法健康雄性SD大鼠130只随机分为假手术组（ SO组，n＝10）、局灶性脑缺血再灌注组（ MCAO组，n＝60）、缺血预处理组（ BIP组，n＝60），MCAO组和BIP组又分别分为再灌注2 h、6 h、12 h、24 h、48 h、72 h 6个亚组，每亚组10只大鼠。采用线栓法制备大鼠脑缺血再灌注模型。 BIP组在缺血前24 h给予10 min的预缺血。采用免疫组化染色法检测HIF－1α、存活素的阳性细胞数。采用Western blot法检测HIF－1α、存活素的蛋白相对含量。结果与SO组比较，MCAO组和BIP组各时间点亚组大鼠缺血侧海马CA1区HIF－1α及存活素的阳性细胞数及蛋白相对含量均明显升高（均P＜0．05）。与MCAO组比较，BIP组各时间点亚组大鼠缺血侧海马CA1区HIF－1α及存活素的阳性细胞数及蛋白相对含量均明显升高（均P＜0．05）。在MCAO组和BIP组中，大鼠缺血侧海马CA1区HIF－1α及存活素的阳性细胞数及蛋白相对含量均在再灌注24 h时达到最高峰（均P＜0．05）。结论缺血预处理能够诱导局灶性脑缺血再灌注大鼠缺血侧海马CA1区HIF－1α、存活素表达上调，这或许与脑缺血耐受的产生机制有关。