β-arrestin 2对多巴胺能神经元的保护作用及机制研究  被引量:2

The protective effect and mechanism of β-arrestin 2 on primary dopaminergic neurons

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作  者:胡丹[1] 熊婧[1] 刘志超[1] Hu Dan;Xiong Jing;Liu Zhiehao(Department of Neurology,Renmin Hospital of Wuhan University,Wuhan 430060)

机构地区:[1]武汉大学人民医院神经内科,430060

出  处:《卒中与神经疾病》2018年第6期625-629,共5页Stroke and Nervous Diseases

基  金:国家自然科学基金青年基金项目(81401051)

摘  要:目的探讨β-arrestin 2对多巴胺能神经元的保护作用及机制。方法分离并培养原代小鼠中脑小胶质细胞,脂多糖(LPS)处理后采用实时定量PCR检测炎性细胞因子IL-6、IL-1β和TNF-α的转录水平,ELISA检测上述因子的表达水平;将原代小鼠中脑小胶质细胞和多巴胺能神经元Transwell共培养(细胞数2∶1),LPS处理后TUNEL法检测多巴胺能神经元凋亡,酪氨酸羟化酶(TH)免疫组织化学法检测多巴胺能神经元。结果原代小胶质细胞经LPS处理后IL-6、IL-1β和TNF-α的转录水平及表达水平均较对照组显著升高,而β-arrestin 2高表达能抑制这种炎症反应;β-arrestin 2高表达能显著抑制LPS处理所致的多巴胺能神经元凋亡,抑制多巴胺能神经元数目的减少。结论β-arrestin 2可能通过抑制小胶质细胞炎性细胞因子的产生,从而对多巴胺能神经元发挥神经保护作用。Objective To investigate the protective effect and mechanism of β-arrestin 2 on dopaminergic neurons.Methods Primary mouse microglial cells were isolated from the midbrain and cultured in vitro.After lipopolysaccharides(LPS)treatment,the transcriptional levels and expression levels of inflammatory cytokines (IL-6,IL-1βand TNF-α) released by microglial cells were examined by real-time quantitative PCR and ELISA respectively.Then primary microglial cells and dopaminergic neurons (2∶1) were co-cultured in the transwell system.Apoptosis was tested by the method of TUNEL and dopaminergic neurons were demonstrated by tyrosine hydroxylase (TH) immunohistochemostry.Results The transcriptional levels and expression levels of inflammatory cytokines including IL-6,IL-1β and TNF-αproduced by microglial cells were significantly increased after LPS treatment.Overexpression of β-arrestin 2 could distinctly inhibit this inflammatory response.Additionally overexpression of β-arrestin 2 also obviously disturbed LPS-induced apoptosis and loss of dopaminergic neurons in the transwell system.Conclusion β-arrestin 2 could exert a neuroprotective effect on dopaminergic neurons probably by inhibiting the production of inflammatory cytokines by microglial cells.

关 键 词:Β-ARRESTIN 2 帕金森病 多巴胺能神经元 小胶质细胞 炎性细胞因子 

分 类 号:R742.5[医药卫生—神经病学与精神病学]

 

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