α-synuclein对多巴胺能神经元凋亡和氧化损伤影响  

EFFECTS OF A-SYNUCLEIN ON APOPTOSIS AND OXIDATIVE DAMAGE OF DOPAMINERGIC NEURONS

作　　者：王静[1] 苏东风 李岩松 邰旭辉 李迪[1] 刘雨萌 WANG Jing;SU Dongfeng;LI Yansong;TAI Xuhui;LI Di;LIU Yumeng(Department of Neurology,Northern Air Force Hospital,Shen-yang 110042,China)

机构地区：[1]中国人民解放军北部战区空军医院神经内科,辽宁沈阳110042 [2]中国人民解放军北部战区空军医院耳鼻喉科,辽宁沈阳110042

出　　处：《青岛大学学报（医学版）》2021年第1期95-99,共5页Journal of Qingdao University(Medical Sciences)

基　　金：辽宁省科学技术计划项目(201602760)。

摘　　要：目的探讨α-共核蛋白(α-synuclein)对多巴胺能神经元凋亡、氧化损伤和炎症的调节作用。方法用H 2 O 2诱导MES23.5细胞的氧化损伤,并在MES23.5细胞中过表达α-synuclein。用谷胱甘肽(GSH)来抵抗MES23.5细胞氧化损伤。采用流式细胞术检测细胞凋亡,分别采用相关试剂盒检测活性氧(ROS)、超氧化物歧化酶(SOD)、白细胞介素(IL)-6、IL-1β和肿瘤坏死因子-α(TNF-α)的水平,以Western blot法检测细胞中B淋巴细胞瘤-2基因蛋白(Bcl-2)和Bcl-2相关x蛋白(Bax)表达。结果过表达α-synuclein可提高MES23.5细胞凋亡率和ROS、IL-6、IL-1β及TNF-α水平,抑制细胞中的SOD活力(F=188.54~315.52,P<0.05)。H 2 O 2可诱导α-synuclein过表达的MES23.5细胞中α-synuclein的表达、细胞凋亡率和ROS活力增加(F=196.49~251.74,P<0.05)。GSH处理α-synuclein过表达的MES23.5细胞后,α-synuclein表达降低,凋亡率和ROS活力降低(F=149.25~258.96,P<0.05)。结论氧化损伤能够增强α-synuclein促进的细胞凋亡和炎症反应,从而放大多巴胺能神经元的氧化损伤。Objective To investigate the regulatory effects ofα-synuclein on the apoptosis,oxidative damage,and inflammation of dopaminergic neurons.Methods We overexpressedα-synuclein in MES23.5 cells,and used H 2O 2 to induce oxidative damage and glutathione(GSH)to resist oxidative damage in MES23.5 cells.Flow cytometry was used to detect cell apoptosis.Test kits were applied to measure the levels of reactive oxygen species(ROS),superoxide dismutase(SOD),interleukin(IL)-6,IL-1β,and tumor necrosis factor-α(TNF-α).Western blot was used to determine the expression of B-cell lymphoma-2 protein and B-cell lymphoma-2-associated x protein.Resultsα-Synuclein overexpression increased the apoptosis rate,upregulated the levels of ROS,IL-6,IL-1β,and TNF-α,and inhibited the activity of SOD in MES23.5 cells(F=188.54-315.52,P<0.05).H 2O 2 increasedα-synuclein expression,the apoptosis rate,and the activity of ROS inα-synuclein-overexpressed MES23.5 cells(F=196.49-251.74,P<0.05).GSH decreased the expression ofα-synuclein,the apoptosis rate,and the activity of ROS inα-synuclein-overexpressed MES23.5 cells(F=149.25-258.96,P<0.05).Conclusion Oxidative damage can enhanceα-synuclein-mediated apoptosis and inflammatory response,which further amplifies the oxidative injury of dopaminergic neurons.

关 键 词：Α-共核蛋白 多巴胺能神经元 氧化还原酶类 细胞凋亡 帕金森病 

分 类 号：R322.8[医药卫生—人体解剖和组织胚胎学] R345.4[医药卫生—基础医学]