星形胶质细胞糖原动员改善大脑缺血再灌注损伤的研究

摘要 目的：探讨星形胶质细胞糖原动员是否对大脑缺血再灌注损伤有神经保护作用。方法：研究构建了星形胶质细胞特异性糖原分解代谢关键酶糖原磷酸化酶（Glycogen phosphorylase, GP）过表达转基因小鼠（GFAP-GP），并通过免疫荧光染色对GP的含量进行验证。在小鼠大脑中动脉梗死/再通模型中，利用GFAP-GP小鼠促进再灌注后累积糖原的分解（糖原动员），通过三苯基氯化四氮唑（Triphenyl tetrazolium chloride, TTC）染色分析再灌注后GFAP-GP小鼠的脑梗死面积，Corner test和Grid-walking test检测再灌注后GFAP-GP小鼠的神经行为学功能。结果：GFAP-GP小鼠中GP的含量发生了明显的增加，再灌注后GFAP-GP小鼠与野生型小鼠相比，脑糖原含量明显降低，梗死明显减少，肢体感觉与运动功能明显改善。结论：星形胶质细胞糖原动员可改善大脑缺血再灌注损伤。

Experimental Study of Glycogen Mobilization Mediated Neuroprotection on Cerebral Ischemia/reperfusion Injury

ABSTRACT Objective: To investigate whether astrocytic glycogen mobilization mediates neuroprotection on cerebral ischemia/reperfusion injury. Methods: This study constructed the astrocyte-specific glycogen phosphorylase (GP) transgenic mice (GFAP-GP), which was verified by immunofluorescence. Using GFAP-GP as a model of glycogen mobilization, the infarct volumes of GFAP-GP were analyzed by TTC staining and the neurobehavioral function was analyzed by Corner test and Grid-walking test after cerebral middle artery occlusion/reperfusion. Results: The GP expression was upregulated in GFAP-GP mice. The glycogen level was down-regulated, the infarct volume was decreased and the neurobehavior performance was improved in the GFAP-GP mice compared with the wild-type mice. Conclusion: Astrocytic glycogen mobilization has neuroprotective effects on ischemia/reperfusion injury.