电针通过cGAS-STING通路影响小胶质细胞介导的带状疱疹后神经痛  

Electroacupuncture affects microglia-mediated postherpetic neuralgia via the cGAS-STING pathway

作　　者：辛欢 邹璟[1] 乐薇[1] XIN Huan;ZOU Jing;LE Wei(Acupuncture and Moxibustion Department,Wuhan First Hospital,Wuhan 430022,China)

机构地区：[1]武汉市第一医院针灸科,武汉430022

出　　处：《中国医科大学学报》2025年第3期208-213,218,共7页Journal of China Medical University

基　　金：国家自然科学基金(82105008)。

摘　　要：目的探讨电针(EA)通过环鸟苷酸-腺苷酸合酶(cGAS)-干扰素基因刺激因子(STING)影响小胶质细胞介导的带状疱疹后神经痛(PHN)的机制。方法将50只大鼠随机分为Vehicle组、树脂素(RTX)组、RTX+EA组、RTX+cGAS抑制剂(RU.521)组、RTX+STING抑制剂(C-176)组,每组10只。通过旷场实验、斜板实验、悬尾实验、机械退缩阈值检测对各组大鼠进行行为学评估,ELISA检测P物质(SP)、神经激肽1(NK-1)、肿瘤坏死因子α(TNF-α)、一氧化氮合酶(iNOS)、白细胞介素-10(IL-10)、精氨酸酶1(Arg1)的表达水平,TUNEL染色检测细胞凋亡情况,免疫荧光染色检测脊髓背角组织中Iba1、cGAS、STING水平,Western blotting检测cGAS-STING通路相关因子的表达。结果与Vehicle组比较,RTX组大鼠焦虑行为增加、运动功能降低、抑郁加重、机械退缩阈值降低,脊髓背角组织中疼痛递质相关因子水平增加、细胞凋亡增加、小胶质细胞激活并向M1极化且激活cGAS-STING通路,EA或cGAS-STING抑制剂则部分逆转上述结果,使小胶质细胞向M2极化(均P<0.05)。结论EA可能通过抑制小胶质细胞中cGAS-STING通路发挥对PHN的治疗作用。Objective To explore the mechanism by which electroacupuncture(EA)affects postherpetic neuralgia(PHN)through the cyclic cGMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway in microglia-mediated processes.Methods Fifty rats were randomly divided into the following groups,with 10 rats in each group:Vehicle group,resiniferatoxin(RTX)group,RTX+EA group,RTX+cGAS inhibitor(RU.521)group,and RTX+STING inhibitor(C-176)group.Behavioral assessments were conducted on rats in each group using the hot plate test,inclined plane test,tail suspension test,and mechanical withdrawal threshold test.The ELISA method was used to detect the levels of substance P(SP),neurokinin 1(NK-1),tumor necrosis factor-α(TNF-α),inducible nitric oxide synthase(iNOS),interleukin-10(IL-10),and arginase 1(Arg1).TUNEL staining was used to detect cell apoptosis,and immunofluorescence staining was used to detect the levels of Iba1,cGAS,and STING in the spinal dorsal horn tissues.Furthermore,Western blotting was used to detect the expression of cGAS-STING pathway-related factors.Results Compared with the Vehicle group,rats in the RTX group exhibited increased anxious behavior,decreased motor function,exacerbated depression,and reduced mechanical withdrawal thresholds.Additionally,there was an increase in the levels of pain-related neurotransmitters,enhanced cellular apoptosis,activation and M1 polarization of microglia in the spinal dorsal horn tissue,and activation of the cGAS-STING pathway.EA or cGAS-STING inhibitors partially reversed the above results and induced M2 polarization of microglia(all P<0.05).Conclusion EA may exert therapeutic effects on PHN by inhibiting the cGAS-STING pathway in microglia.

关 键 词：电针 环鸟苷酸-腺苷酸合酶 干扰素基因刺激因子 小胶质细胞 带状疱疹后神经痛 

分 类 号：R752.1[医药卫生—皮肤病学与性病学]