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目的 探讨细胞周期蛋白抑制物P2 7kipl在NPC小鼠模型中神经元变性、死亡及星形胶质细胞增生中的作用。方法 利用免疫组化和免疫荧光技术检测NPC 1小鼠脑部P2 7kipl表达及胶质细胞增殖的情况。结果 P2 7pipl在野生型小鼠大脑皮质、海马、基底节、脑干广泛的神经元及小脑Purkinje细胞均有较强的表达 ,而且在部分胶质细胞也存在免疫反应性 ,而在NPC小鼠的基底节、脑干神经元及小脑Purkinje细胞中P2 7kipl的表达明显弱于野生型小鼠。GFAP阳性星形胶质细胞出现P2 7kipl表达上调 ,其细胞数在NPC小鼠大脑皮质、海马及脑干 (尤其在桥脑处 )显著增多 ,提示星形胶质细胞异常增生。结论 在NPC小鼠中枢神经元发生病变的同时 ,星形胶质细胞也发生了明显的病理性增生 ,细胞周期蛋白酶抑制物P2 7kipl失调参与了这一病理过程
Objective To investigate the role of cyclin P2 7 kipl in neuronal degeneration, death and astrocyte proliferation in NPC mouse models. Methods Immunohistochemistry and immunofluorescence were used to detect the expression of P2 7 kipl and the proliferation of glial cells in the brain of NPC1 mice. Results P2 7pipl showed strong expression in the cerebral cortex, hippocampus, basal ganglia and cerebellum of Purkinje cells in wild-type mice, and also immunoreactive in some glial cells. However, in NPC mice The basal ganglia, brainstem neurons and cerebellum Purkinje cells P2 7kipl expression was significantly weaker than the wild-type mice. The expression of P2 7kipl in GFAP positive astrocytes was up-regulated. The number of GFAP positive astrocytes was significantly increased in the cerebral cortex, hippocampus and brainstem of NPC mice, especially in the pons. This indicated that astrocytes proliferated abnormally. Conclusions In the development of central nervous system of NPC mouse, pathological hyperplasia also occurs in astrocytes, and P2 7kipl, a cyclin inhibitor, is involved in this pathological process