C型Niemann-Pick病小鼠P27kipl表达异常与神经元变性和星形胶质细胞增生

目的探讨细胞周期蛋白抑制物P27kipl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P27kipl表达及胶质细胞增殖的情况.结果 P27pipl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P27kipl的表达明显弱于野生型小鼠.GFAP阳性星形胶质细胞出现P27kipl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P27kipl失调参与了这一病理过程.

Deregulation of P27kipl is related with neuronal degeneration and astrocytosis in a mouse model of Niemann-Pick disease type C

Objective To study the expression of P27 kipl in brain tissues of Niemann Pick disease type C(NPC) mice.Methods The expressions of P27 kipl in the brains of NPC mice and wild type mice were investigated with immunohistochemical methods.Results The expression of P27 kipl in the astrocytes in different parts of NPC mouse brains was much higher than that in wild mice, but in the neurons of NPC mouse brains, P27 kipl immunostaining was much weaker than in the wild mice.The astrocytosis in NPC mouse brains was obviously present, compared with the wild mice ( P < 0.05 ).The immunoreactivity of P27 kipl in Purkinje cells of NPC mouse brains was very faint, and most Purkinje cells were lost as well ( P < 0.05 ).Conclusions The data that the deregulation of P27 kipl in NPC mouse brains suggest that P27 kipl may get involved in the proliferation of astrocytes and neuronal degeneration and death.The detailed rules of P27 kipl in NPC pathogenesis still remain to be elucidated.