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目的 观察细胞周期调控对大鼠全脑缺血再灌流后海马区迟发性神经元死亡 (delayed neuronal death,DND) 以及星形胶质细胞的活化、增殖的影响。方法 建立大鼠短暂性全脑缺血再灌流模型, 利用尼氏染色、TUNEL、免疫组织化学方法观察再灌流后细胞周期素依赖的蛋白激酶 (cyclin depedent kinase, CDK) 抑制剂 Olomoucine 对海马DND以及星形胶质细胞活化增殖的影响。结果 全脑缺血再灌流后 3d、7d、30d海马神经元明显脱失, 部分 CA1、CA2区神经元凋亡; 星形胶质细胞数目增多, GFAP表达上调, 应用Olomoucine后TUNEL阳性神经元数目明显减少, 幸存神经元数目增加; 星形胶质细胞数目无明显增多, GFAP表达明显下调。结论 CDK抑制剂 Olomoucine可有效抑制大鼠全脑缺血后海马神经元DND以及星形胶质细胞活化增殖。
Objective To observe the effects of cell cycle regulation on delayed neuronal death (DND) and activation and proliferation of astrocytes in rats after global cerebral ischemia and reperfusion. Methods A rat model of transient global cerebral ischemia-reperfusion was established. Nissl staining, TUNEL and immunohistochemistry were used to observe the effect of Olomoucine, a cyclindependent kinase inhibitor of hippocampus, on DND in hippocampus and Effect of Astrocyte Activation and Proliferation. Results Neurons in hippocampus of rats in group CA1 and CA2 were significantly lost after 3d, 7d and 30d after global cerebral ischemia-reperfusion. The number of astrocytes increased and the expression of GFAP was up-regulated. The number of TUNEL-positive neurons after Olomoucine Significantly decreased, and the number of surviving neurons increased; the number of astrocytes was not significantly increased, GFAP expression was significantly down-regulated. Conclusion Olomoucine, a CDK inhibitor, can effectively inhibit the activation of DND and astrocyte in hippocampal neurons after global cerebral ischemia in rats.