蛋白激酶Cδ在6-OHDA诱导大鼠多巴胺能神经元损伤过程中的作用  

The role of PKCδ in 6-OHDA-induced dopaminergic neurons damage in rats

作　　者：韩飞 夏克明 杨斌 李成朋 吴昌学[3] 禹文峰 Han Fei;Xia Kerning;Yang Bin;Li Chengpeng;Wu Changxue;Yu Wenfeng(Guizhou Orthopaedic Hospital,Guiyang 550007;Department of Pharmacy,Guizhou University,Guiyang 550025;Key Laboratory of Endemic and Ethenic Diseases Ministry of Education,Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州省骨科医院,贵阳550007 [2]贵州大学药学院,贵阳550025 [3]贵州医科大学地方病与少数民族性疾病教育部重点实验室,贵阳550004

出　　处：《神经解剖学杂志》2021年第3期323-328,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81360199)。

摘　　要：目的:探究蛋白激酶Cδ(PKCδ)对6-羟基多巴胺(6-OHDA)诱导的帕金森病(PD)模型大鼠多巴胺能神经元损伤的影响及其机制。方法:50只2月龄雄性SD大鼠,随机分为对照组(control)和6-羟基多巴胺注射组(6-OHDA)。通过大鼠右侧纹状体注射6-OHDA溶液构建PD模型。运用旋转实验和圆筒实验检测平均旋转速率和右上肢使用率,利用免疫组化染色观察大鼠黑质致密部(SNc)酪氨酸羟化酶(TH)的表达,利用Western Blot检测大鼠SNc部位线粒体中PKCδ和胞质中细胞色素c(Cyt c)及TH的表达情况,通过免疫荧光染色观察PKCδ定位。结果:6-OHDA组大鼠平均旋转速率及右上肢使用率明显增加,TH阳性神经元形态及分布异常且TH蛋白表达减少,线粒体PKCδ表达增多,胞质中Cyt c增多,免疫荧光染色显示PKCδ与线粒体蛋白发生共定位现象。结论:PKCδ可能通过线粒体转移参与调节6-OHDA诱导的大鼠多巴胺能神经元损伤。Objective:To study the effects of protein kinase Cδ(PKCδ)in the injury of dopaminergic neurons and its mechanism in Parkinson’s disease(PD)rat model induced by 6-hydroxy dopamine(6-OHDA).Methods:fifty twomonth SD rats were randomly grouped as control group(control)and 6-OHDA injected group(6-OHDA).6-OHDA solution was injected unilaterally in striatum to construct PD models.Rotation experiment and cylinder experiment were adopted for test the rotation rate and usage rate of right upper limb.The expression of tyrosine hydroxylase(TH)in substantia nigra pars compacta(SNc)was observed by immunohistochemical staining.Expression of PKCδin mitochondria and cytochrome c(Cyt c)together with TH in cytosolic of SNc were detected by Western Blot.Immunofluorescence technique was used for observe the localization of PKCδ.Results:Rotation rate and the usage rate of right upper limb were significantly increased in 6-OHDA group.TH-positive neurons were distributed abnormally,while the TH protein was less expression in 6-OHDA group.PKCδin mitochondria and cytoplasmic Cyt c were up-regulated in the SNc of6-OHDA injected rats.Immunofluorescence technique showed the co-localization between PKCδand mitochondrial protein.Conclusion:Mitochondrial translocation of PKCδmay participated in the injury of dopaminergic neurons in rat model induced by 6-OHDA.

关 键 词：蛋白激酶Cδ 线粒体转位 6-羟基多巴胺 帕金森病 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学]