脑缺血后处理对脑缺血再灌注大鼠Notch1信号通路及学习记忆功能的影响

The Effect of Ischemic Postconditioning on the Notch1 Signaling Pathway and Learning and Memory in Rats with Cerebral Ischemia Reperfusion Injury

目的探讨脑缺血后处理(CIP)对全脑缺血大鼠Notch1信号通路及其学习记忆功能的影响。方法将128只健康的雄性SD大鼠随机分为假手术组(sham组)、脑缺血再灌注模型组(CIR组)、脑缺血后处理组(CIP组)、抑制剂组(DAPT组),每组32只。采用改良的Pulsinelli四血管阻断法制备全脑缺血模型;DAPT组是在实施CIP前腹腔注射γ分泌酶抑制剂(DAPT)。Morris水迷宫测试检测大鼠学习记忆功能,HE染色观察海马CA1区神经细胞形态变化;免疫组织化学法、Western blotting法检测大鼠脑组织海马CA1区Notch1在海马区的表达情况。结果与sham组比较,CIR组海马区存活细胞率显著降低(P<0.05),Notch1阳性细胞数及Notch1蛋白的表达水平明显升高(P<0.05);与CIR组比较,CIP组海马区存活细胞率显著升高(P<0.05),Notch1阳性细胞数及Notch1蛋白的表达水平明显升高(P<0.05);与CIP组比较,DAPT组海马区存活细胞率显著降低(P<0.05),Notch1阳性细胞数及Notch1蛋白的表达水平明显降低。结论 CIP可促进脑缺血再灌注大鼠学习记忆功能恢复,其机制可能与激活Notch1信号通路有关。

Objective To assess the effect of ischemic postconditioning on the Notchl signaling pathway,and learning and memory in rats with global cerebral ischemia. Methods A total of 128 healthy male SD rats were randomly divided into the sham operation （sham）, whole-brain ischemia（CIR）, ischemic treatment（CIP）, and inhibitor（DAPT） groups ,with 32 rats in each group. A global cerebral ischemia model was generated using the modified Pulsinelli＇s four-vascular occlusion model, and the inhibitor group was injected intraperitoneally with gamma secretase inhibitors （DAPT） before ischemic treatment. Rats＇ learning and memory function results from the Morris water maze test were assessed by observing the changes in hippocampal CAI neurons with HE staining. The expression of Notchl in the CAI area of the hippocampus was assessed using immunohistochemical and Western blotting methods in rats. Results Compared with the sham group,the hippocampal cell survival rate in the CIR group decreased significantly （P 〈 0.05） and the expression level of Notchl increased significantly （P 〈 0.05）. Compared with the CIR group, the CIP group revealed a significantly higher hippoealnpal cell survival rate （P 〈 0.05） and an increase in Notchl expression （P 〈 0.05） ：compared with the CIP group,the hippocampal cell survival rate significantly decreased after DAPT administration （P 〈 0.05） and Notchl expression decreased significantly. Conclusion Ischemic postconditioning can promote the recovery of learning and memory ability, which may relate to the activation of the Notch 1 signaling pathway.