脑缺血预处理中大鼠海马Notch信号通路的变化

目的:探讨脑缺血预处理诱导大鼠脑缺血耐受中Notch信号通路的变化。方法:成年雄性SD大鼠60只,随机分为2组(n=30):正常对照组(C组)脑缺血再灌注前不做任何处理;脑缺血预处理组(P组)于脑缺血前24 h栓塞右大脑中动脉20 min后使血流再灌注一次。采用阻断单侧大脑中动脉120 min再灌注24 h的方法制备局灶性脑缺血再灌注模型。分别于缺血前、再灌注24 h时采用Western blot法测定右侧海马Notch细胞内片段(NICD)蛋白的表达,采用实时定量PCR法测定右侧海马Notch通路信号分子的表达;再灌注24 h时进行神经功能损伤评分,评分完毕后测定脑梗死体积百分比。结果:与C组比较,缺血前P组大鼠海马NotchlmRNA、Notch4mRNA和NICD蛋白表达上调(P<0.05);与缺血前比较,两组再灌注24 h时NICD蛋白表达上调;与C组比较,P组再灌注24 h时NICD蛋白表达下调,脑梗死体积百分比降低,神经功能损伤评分降低(P<0.05)。结论:Notch信号通路可能与脑缺血预处理诱导的大鼠脑缺血耐受有关。

The changes of Notch signaling in hippocampus after cerebral ischemic precondition

Objective: To investigate the changes of Notch signaling pathway in cerebral ischemic tolerance induced by cerebral ischemic preconditioning.Methods: Sixty adult male SD rats were randomly divided into 2 groups(n = 30) : normal control group(group C) and cerebral ischemic preconditioning group(group P).Group C received no treatment. Group P received cerebral ischemic preconditioning with the right middle cerebral artery occlusion for 20 min,followed by 24 h of reperfusion.Cerebral ischemia and reperfusion mode was induced by unilateral middle cerebral artery occlusion for 120 min,followed by 24 h of reperfusion.Notch intracellular domain(NICD) protein expression was determined by Western blot and expression of the Notch pathway signaling molecules of right hippocampus by real-time quantitative PCR before ischemia and 24h of reperfusion.The neurological deficit score was graded at 24 h of reperfusion.The infarct volumes were then determined after evaluation of the neurological deficit score.Results: Compared with group C,the protein expression of Notch1mRNA,Notch4mRNA and NICD were up-regulated in group P before ischemia(P < 0.05);NICD expression was up-regulated at 24 h of reperfusion compared before ischemia in both groups.Compared with group C, NICD expression was down-regulated,the percentage of infarct volume and neurological deficit score was decreased at 24 h of reperfusion in group P(P < 0.05).Conclusion: Notch signaling pathway may be associated with brain ischemic tolerance induced by cerebral ischemic preconditioning.