MicroRNA-124对帕金森病中多巴胺能神经元的神经保护作用  

Neuroprotective effect of microRNA-124 on dopaminergic neurons in Parkinson ＇ s disease models

作　　者：卢国辉[1] 蒋春梅[2] 肖振勇[1] 张世忠[1] 

机构地区：[1]南方医科大学珠江医院神经外科,广东神经外科研究所,广东省脑功能修复与再生重点实验室,广州510280 [2]广州医学院荔湾医院风湿科,广州510170

出　　处：《中华神经医学杂志》2013年第3期226-230,共5页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金（81172416）;国家临床重点建设专科资助项目

摘　　要：目的研究microRNA（miR）．124对帕金森病模型小鼠中脑多巴胺能神经元的神经保护作用．并探讨其免疫炎性调控机制。方法采用小胶质细胞系BV2细胞制备炎性反应的细胞模型．实时荧光定量PCR（qRT-PCR）检测miR-21、miR-124、miR．155、miR-146a、miR．18lc、miR-221．3p等中枢炎性相关miRNAs表达；腹腔内注射1．甲基一4一苯基．1，2，3，6．四氢吡啶（MPTP）制备帕金森病小鼠模型，尾静脉注射miR-124治疗，免疫组织化学染色观察治疗前后多巴胺能神经元凋亡情况（TH蛋白表达）、小胶质细胞活化情况（Ibal蛋白表达），Westernblotting及qRT—PCR检测治疗前后细胞凋亡相关蛋白酶caspase-3、caspase-8的表达情况。结果miR-124在BV2细胞中表达量明显高于其他5种miRNAs，差异有统计学意义（氏0．05），且致炎后表达下调幅度最大；与帕金森病模型鼠相比，miR-124治疗后黑质区TH阳性细胞数明显增多，而lbal阳性细胞数明显减少，caspase-3、caspase-8的表达量亦明显减少，差异有统计学意义（P〈0．05）。结论miR-124可通过抑制黑质区小胶质细胞活性缓解多巴胺能神经元凋亡进程，可能是帕金森病发病机制中的一个关键因子。Objective To investigate the neuroprotective effect of microRNA-124 on dopaminergic neurons in Parkinson＇s disease models and its inflammation-related regulation mechanism. Methods The inflammation cell models were prepared by microglial BV2 murine cells; real-time quantitative PCR （qRT-PCR） was performed to analyze the expressions of inflammation-related miRNAs, including miR-21, miR-124, miR-155, miR-146a, miR-181c and miR-221-3p. The C57BL/6 mouse models of Parkinson＇s disease were established by 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine （MTPT） intraperitoneal injection, and then, administration of miR-124 via tail vein injection was performed; immunohistochemistry was performed to observe the apoptosis of dopaminergic neurons （TH-staining） and the activation ofmicroglial cells （Ibal-staining） in the substantia nigra of animal models before and after treatment; additionally, Western blotting and qRT-PCR were performed to analyze the expressions of the apoptosis-related proteins （caspase-3 and caspase-8）. Results As compared with other 5 miRNAs, miR-124 showed significantly higher expression in BV2 cells （P〈0.05）, and presented higher down-regulation after the induction of inflammatory. As compared with those in the Parkinson＇s disease models, significantly increased TH-positive cells, decreased Ibal-positive cells and down-regulated expressions of caspase-3 and caspase-8 in the substantia nigra of animal models after miR-124 ministration were observed （P〈0.05）. Conclusion MiR-124 can slow down the apoptosis of dopaminergic neurons though inhibiting the activation of microglial cells, and maybe it is the key molecule ofpathogenesis of Parkinson＇s disease.

关 键 词：MicroRNA-124 帕金森病 多巴胺能神经元 神经保护 

分 类 号：R742.5[医药卫生—神经病学与精神病学]