CX3CR1参与雷公藤内酯对MPP^+帕金森病大鼠多巴胺能神经元的保护作用  

CX3CR1 mediates the neuroprotective effect of triptolide on 1-methyl-4-phenylpyridinium-induced hemiparkinson rats

作　　者：周子懿 高俊鹏[3] 向军[4] 陈依萍[4] 蔡业峰[1,2] 罗恩丽 蔡定芳[4] 

机构地区：[1]广州中医药大学第二附属医院 [2]广东省中医院脑病一科,广东广州510120 [3]广州医科大学附属广州市第一人民医院中医科,广东广州510180 [4]复旦大学附属中山医院中西医结合神经病学研究室,上海200032

出　　处：《中国病理生理杂志》2015年第4期659-663,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81373712)

摘　　要：目的:探讨雷公藤内酯对1-甲基-4-苯基吡啶(MPP+)帕金森病模型大鼠的保护作用及其可能机制。方法:采用MPP+黑质内注射建立帕金森病大鼠模型。实验分为假手术组、模型组、雷公藤内酯组及其溶剂对照组,利用酪氨酸羟化酶(TH)免疫荧光强度测定多巴胺神经元存活率、小胶质细胞标记物OX-42免疫荧光强度测定小胶质细胞激活程度、Western blotting测定趋化因子受体CX3CR1表达量。结果:免疫组化结果表明,MPP+黑质内注射可使模型组OX-42免疫荧光强度增高,DA神经元进行性变性死亡。雷公藤内酯组OX-42免疫荧光强度较模型组低(P<0.01),TH阳性神经元数量较模型组多(P<0.01)。Western blotting结果提示雷公藤内酯组CX3CR1表达量较模型组低(P<0.05)。结论:雷公藤内酯对MPP+帕金森病大鼠模型具有神经保护作用,其机制可能与抑制小胶质细胞激活有关,抑制CX3CR1可能是其抑制小胶质细胞的途径之一。AIM：To investigate the effect of triptolide on the inhibition of microglial activation in 1-methyl-4-phenyl pyridinium （ MPP＋）-induced hemiparkinson disease rats.METHODS：The rat model of Parkinson disease was es-tablished by intranigral injection of MPP ＋.The rats were randomly divided into sham group, MPP＋group, triptolide group and vehicle group.The survival of dopaminergic neurons was detected by the immunofluorescence of tyrosine hydroxylase （ TH） in the substantia nigra （ SN） .The activation of microglia was determined by immunofluorescence of OX-42 （ micro-glia marker） in the SN.The expression of chemokine receptor CX3CR1 in SN was measured by Western blotting.RE-SULTS：Intranigral injection of MPP＋increased the fluorescence intensity of the microglial marker, and promoted DA neu-ron degenerative death.Immunohistological analysis showed that the OX-42 density was decreased （P〈0.01） and tyrosine hydroxylase （TH） positive neurons were increased in the triptolide group （P〈0.01）.The expression of CX3CR1 was lower in triptolide group than that in model group （P〈0.05）.CONCLUSION：Triptolide may improve PA neurons func-tion in MPP＋-induced rats through inhibiting CX3CR1 expression and microglial activation.

关 键 词：帕金森病 小胶质细胞 雷公藤内酯 多巴胺能神经元 

分 类 号：R363[医药卫生—病理学] R741[医药卫生—基础医学]