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

doi:10.3969/j.issn.1006-7795.2018.05.013

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (5): 693-698.doi: 10.3969/j.issn.1006-7795.2018.05.013

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

宫晓丽^1,2,3, 刘梦茹^3,4, 王乐^3,4, 刘玚^3,4, 张婷^3,4, 孙英¹, 王晓民^2,3,4

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

收稿日期:2018-06-12 出版日期:2018-09-21 发布日期:2018-10-20
通讯作者: 孙英, 王晓民 E-mail:ying.sun@ccmu.edu.cn;xmwang@ccmu.edu.cn
基金资助:
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）。

Role of α-synuclein in microglia inflammation and phagocytosis

Gong Xiaoli^1,2,3, Liu Mengru^3,4, Wang Le^3,4, Liu Yang^3,4, Zhang Ting^3,4, Sun Ying¹, Wang Xiaomin^2,3,4

1. Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
2. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
3. Key Laboratory of Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China;
4. Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

Received:2018-06-12 Online:2018-09-21 Published:2018-10-20
Supported by:
This study was supported by Major Program of National Natural Science Foundation of China (81527901), National Key Research and Development Program (2016YFC1306300), Natural Science Foundation of Beijing (7162019), National Major Research and Development Program of Beijing Municipal Science & Technology Commission (Z161100002616007).

摘要/Abstract

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，RT-qPCR）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。

关键词: α-突触核蛋白, 吞噬, 炎性反应

Abstract: Objective Our study observed the effect of α-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 of α-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 the α-syn induced inflammatory response. Results Twenty-four hours after α-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-α and IL-1β, and the release of TNF-α stimulated by α-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.

Key words: α-synuclein, phagocytosis, inflammation

中图分类号:

R741.02

宫晓丽, 刘梦茹, 王乐, 刘玚, 张婷, 孙英, 王晓民. 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[J]. 首都医科大学学报, 2018, 39(5): 693-698.

Gong Xiaoli, Liu Mengru, Wang Le, Liu Yang, Zhang Ting, Sun Ying, Wang Xiaomin. Role of α-synuclein in microglia inflammation and phagocytosis[J]. Journal of Capital Medical University, 2018, 39(5): 693-698.

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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

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