α-突触核蛋白在小胶质细胞炎性反应和吞噬功能中的作用研究  

Role of α-synuclein in microglia inflammation and phagocytosis

作　　者：宫晓丽[1,2,3] 刘梦茹 王乐[3,4] 刘玚[3,4] 张婷 孙英[1] 王晓民[2,3,4] Gong Xiaoli;Liu Mengru;Wang Le;Liu Yang;Zhang Ting;Sun Ying;Wang Xiaomin(Department of Immunology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;Key Laboratory of Neurodegenerative Disorders of the Ministry of Education,Capital Medical University,Beijing 100069,China;Department of Neurobiology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学基础医学院免疫学系,北京100069 [2]首都医科大学基础医学院生理学与病理生理学系,北京100069 [3]首都医科大学教育部神经变性病重点实验室,北京100069 [4]首都医科大学基础医学院神经生物学系,北京100069

出　　处：《首都医科大学学报》2018年第5期693-698,共6页Journal of Capital Medical University

基　　金：国家自然科学基金重点项目(81527901);国家重点研究与发展计划(2016YFC1306300);北京市自然科学基金(7162019);北京市科学技术委员会国家重大研发计划(Z161100002616007)~~

摘　　要：目的本研究对比观察中枢神经系统中α-突触核蛋白(α-synuclein,α-syn)对固有免疫细胞小胶质细胞的炎性反应和吞噬功能的影响。方法离体培养原代小胶质细胞,给予不同浓度的α-syn蛋白或阳性对照细菌脂多糖(lipopolysaccharides,LPS)刺激,利用荧光微球吞噬实验和溶酶体相关蛋白分化抗原68(clusters of differentiation 68,CD68)的荧光染色实验来观察细胞吞噬功能的改变;利用反转录实时定量聚合酶链反应(reverse transcription-quantitative real-time polymerase chain reaction,RTq PCR)实验观察肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1 beta,IL-1β)等炎性反应因子的表达,评价α-syn或LPS诱导的炎性反应水平。结果α-syn刺激24 h后,小胶质细胞吞噬荧光微球的数目明显增多、CD68表达增加,与LPS作用效果相似。但α-syn对炎性反应因子TNF-α和IL-1β转录水平的改变,以及TNF-α的释放却远低于LPS。结论α-syn可明显增强小胶质细胞的吞噬功能,但对其炎性反应水平影响较小。Objective Our study observed the effect ofα-synuclein(α-syn)on inflammation and phagocytosis of microglia which are the resident immune cells in central nervous system.Methods Primary microglia cultured in vitro were treated by different concentrations ofα-syn or lipopolysaccharides(LPS).Then the changes of phagocytosis of microglia were observed by fluorescent microspheres and fluorescent staining with clusters of differentiation 68(CD68)proteins.The expression of inflammatory factors,tumor necrosis factor-α(TNF-α)and interleukin-1 beta(IL-1β),were detected by reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)to observe theα-syn induced inflammatory response.Results Twenty-four hours afterα-syn stimulation,the number of microspheres that ingested in cells and CD68 expression increased significantly,similar to that with LPS treatment.However,both the changes of transcription level of inflammatory factors,TNF-αand IL-1β,and the release of TNF-αstimulated byα-syn were much lower than those by LPS.Conclusion α-syn can significantly enhance the phagocytosis of microglia,but has little effect on inflammatory response.

关 键 词：Α-突触核蛋白 吞噬 炎性反应 

分 类 号：R741.02[医药卫生—神经病学与精神病学]