毛蕊花糖苷调节STING/TBK1/IRF3信号通路对帕金森病小鼠神经炎症的影响  

Effect of verbascoside on neuroinflammation in Parkinson's disease mice by regulating STING/TBK1/IRF3 signaling pathway

作　　者：郭敏[1] 李佳[1] 贺冠强[1] 庞旭阳 王旭东[1] 朱海生[1] 李晓蕾[1] 房娉平[1] Guo Min;Li Jia;He Guanqiang;Pang Xuyang;Wang Xudong;Zhu Haisheng;Li Xiaolei;Fang Pingping(Third Department of Neurology,the handan Central Hospital,Hebei 056001,China)

机构地区：[1]邯郸市中心医院神经内三科,河北056001

出　　处：《脑与神经疾病杂志》2025年第4期211-217,共7页Journal of Brain and Nervous Diseases

基　　金：河北省2024年度医学科学研究课题计划(20240788)。

摘　　要：目的探究毛蕊花糖苷调节干扰素基因刺激因子(STING)/TANK结合激酶1(TBK1)/转录因子干扰素调节因子3(IRF3)信号通路对帕金森病(PD)小鼠神经炎症的影响。方法取C57BL/6小鼠通过腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)来建立PD模型,随机分为模型组、毛蕊花糖苷(30mg·kg^(-1))组、Vadimezan(DMXAA)(STING激活剂,36mg·kg^(-1))组、毛蕊花糖苷(30mg·kg^(-1))+DMXAA(36mg·kg^(-1))组,每组10只,另取10只C57BL/6小鼠作为对照组。采用毛蕊花糖苷和DMXAA分组干预后评测小鼠震颤麻痹症状;以转棒实验和爬杆实验评测小鼠运动功能;以免疫组化法检测小鼠大脑黑质区酪氨酸羟化酶(TH)及离子化钙结合适配分子1(Iba1)阳性表达来评测小鼠多巴胺能神经元缺损及胶质细胞激活情况;酶联免疫吸附测定(ELISA)测量小鼠脑组织促炎因子水平;以免疫印迹检测小鼠脑组织STING/TBK1/IRF3信号通路蛋白表达。结果模型组小鼠在棒时间、TH阳性率明显低于对照组(P<0.05),震颤麻痹评分、爬杆时长、Iba1阳性率、脑组织白细胞介素(IL)-6、IL-1及肿瘤坏死因子α(TNF-α)水平、干扰素基因刺激因子(STING)/TANK结合激酶1(TBK1)/转录因子干扰素调节因子3(IRF3)蛋白表达明显高于对照组(P<0.05)。毛蕊花糖苷可改善PD小鼠上述各项病理指标(P<0.05),DMXAA对PD小鼠的作用与毛蕊花糖苷相反(P<0.05),且DMXAA可减弱毛蕊花糖苷对PD小鼠上述各病理指标的影响。结论毛蕊花糖苷可通过抑制STING/TBK1/IRF3信号通路活化传导而阻止PD小鼠胶质细胞激活及神经炎症发生发展,进而减轻其多巴胺能神经元缺损,缓解其震颤麻痹及运动功能损伤症状。Objective To investigate the effect of verbascoside regulate interferon gene stimulator(STING)/TANK-binding kinase 1(TBK1)/transcription factor interferon regulatory factor 3(IRF3)signaling pathway on neuroinflammation in Parkinson's disease(PD)mice.Methods PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in C57BL/6 mice,the mice were randomly divided into model group,acteoside(30mg·kg^(-1))group,vadimezan(DMXAA)(STING activator,36mg·kg^(-1))group,acteoside(30mg·kg^(-1))+DMXAA(36mg·kg^(-1))group,10 mice in each group,another 10 C57BL/6 mice were used as control group.The symptoms of tremor paralysis in mice were evaluated after intervention with verbascoside and DMXAA.The motor function of mice were evaluated by rotating rod experiment and climbing rod experiment.The positive expression of tyrosine hydroxylase(TH)and ionized calcium binding adapter molecule 1(Iba1)in the substantia nigra of the mouse brain to evaluate the dopaminergic neuron defect and glial cell activation in the mouse brain were detected by Immunohistochemistry.The levels of proinflammatory factors in brain tissue of mice were measured by enzyme-linked immunosorbent assay(ELISA).The expression of STING/TBK1/IRF3 signaling pathway protein in mouse brain tissue was detected by immunoblotting.Results The rod time and TH positive rate of mice in model group were significantly lower than those in control group(P<0.05),the tremor paralysis score,rod climbing time,Ibal positive rate,brain tissue interleukin(IL)-6,IL-1 and tumor necrosis factor-α(TNF-α)levels,stimulator of interferon genes(STING)/TANK-binding kinase 1(TBK1)/transcription factor interferon regulatory factor 3(IRF3)protein expression were significantly higher than those in control group(P<0.05).Verbascoside could improve the above pathological indexes of PD mice(P<0.05),the effect of DMXAA on PD mice was opposite to that of verbascoside(P<0.05),and DMXAA could reduce the effect of verbascoside on the above pathological index

关 键 词：毛蕊花糖苷 STING/TBK1/IRF3信号通路 帕金森病 神经炎症 

分 类 号：R742.5[医药卫生—神经病学与精神病学]