电针调控HMGB1/TLR4/NF-κB信号通路影响小胶质细胞活化进而改善带状疱疹后遗神经痛  

Electroacupuncture Affects Microglial Activation and Subsequently Improves Postherpetic Neuralgia via HMGB1/TLR4/NF-κB Signaling Pathway

作　　者：辛欢 邹璟[1] 乐薇 Xin Huan;Zou Jing;Le Wei(Department of Acupuncture and Moribustion,Wuhan Hospital of Traditional Chinese and Western Medicine(Wuhan No.1 Hospital),Tongji Medical College,Huazhong University of Science and Technology+Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属武汉市中西医结合医院(武汉市第一医院)针灸科,武汉430022

出　　处：《华中科技大学学报(医学版)》2025年第2期159-165,共7页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.82105008)。

摘　　要：目的探讨电针(electroacupuncture,EA)通过高迁移率族蛋白B1(high mobility group Box 1,HMGB1)/Toll样受体4(Toll-like receptor 4,TLR4)/核因子κB(nuclear factor kappa-B,NF-κB)通路影响小胶质细胞活化进而改善带状疱疹后遗神经痛(postherpetic neuralgia,PHN)的机制。方法将50只SPF级SD大鼠分为:对照组(Vehicle组)、模型组(RTX组)、假电针组(Sham-EA组)、电针组(EA组)、电针+通路抑制剂组(EA+Gly组)。通过机械退缩阈值检测、热缩足反射潜伏期检测和斜板实验进行大鼠行为学检测。苏木精-伊红(HE)染色检测脊髓背角组织病理形态变化。TUNEL实验检测脊髓背角组织细胞凋亡。ELISA法检测疼痛敏感相关物质前列腺素E2(PGE2)、P物质(SP)、神经激肽1(NK-1)水平,以及炎性因子白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平。免疫荧光法检测Iba1表达。蛋白印迹法检测HMGB1/TLR4/NF-κB通路相关蛋白表达。结果与Vehicle组相比,RTX组大鼠机械退缩阈值降低,热缩足反射潜伏期缩短,在斜板保持平衡的角度减小;脊髓背角组织结构被破坏,神经纤维排列紊乱,出现炎性细胞浸润,细胞凋亡率上升,小胶质细胞活化增多,PGE2、SP、NK-1、IL-6、IL-1β、TNF-α水平升高,HMGB1、TLR4、NF-κB p65蛋白表达上调(均P<0.01)。与RTX组相比,Sham-EA组无显著差异(均P>0.05),EA组大鼠机械退缩阈值升高,热缩足反射潜伏期延长,在斜板保持平衡的角度增大,脊髓背角组织中神经节细胞损伤得到缓解,排列较为整齐,炎性细胞浸润减少,细胞凋亡率降低,小胶质细胞活化减少,PGE2、SP、NK-1、IL-6、IL-1β、TNF-α水平降低,HMGB1、TLR4、NF-κB p65蛋白表达下调(均P<0.01)。与EA组相比,EA+Gly组大鼠机械退缩阈值升高,热缩足反射潜伏期延长,在斜板保持平衡的角度增大,脊髓背角组织中神经细胞损伤和紊乱程度减轻,细胞凋亡率降低,小胶质细胞活化减少,PGE2、SP、NK-1�Objective To explore the mechanism by which electroacupuncture(EA)improves postherpetic neuralgia(PHN)by affecting the activation of microglia through the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB)signaling pathway.Methods Fifty SPF-grade SD rats were divided into the following groups:control(Vehicle)group,model(RTX)group,sham electroacupuncture(Sham-EA)group,electroacupuncture(EA)group,and electroacupuncture+pathway inhibitor(EA+Gly)group.Behavioral tests in rats were conducted using mechanical withdrawal threshold testing,hot foot reflex latency testing,and tilt board testing.Hematoxylin-eosin(HE)staining was used to detect pathological morphological changes in the spinal dorsal horn tissue.TUNEL assay was used to detect cell apoptosis in the spinal dorsal horn tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of pain-sensitive substances:prostaglandin E2(PGE2),substance P(SP),neurokinin 1(NK-1),and inflammatory factors:interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factorα(TNF-α).Immunofluorescence was used to detect the expression of Iba1.Western blot was used to detect the expression of proteins involved in the HMGB1/TLR4/NF-κB pathway.Results Compared with Vehicle group,RTX group showed decreased mechanical withdrawal threshold,shortened hot foot reflex latency,reduced angle of balance on the tilt board,structural damage,disordered arrangement of nerve fibers,inflammatory cell infiltration,increased cell apoptosis rate,increased activation of microglia,and increased levels of PGE2,SP,NK-1,IL-6,IL-1β,TNF-α in the spinal dorsal horn tissue,with upregulated expression of HMGB1,TLR4,NF-κB p65 proteins(all P<0.01).Compared with RTX group,no significant difference was observed in Sham-EA group(P>0.05),while EA group showed increased mechanical withdrawal threshold,prolonged hot foot reflex latency,increased angle of balance on the tilt board,relieved morphological damage of nerve cells,more orderly arrangement,reduced inf

关 键 词：高迁移率族蛋白B1/Toll样受体4/核因子-κB 电针 小胶质细胞活化 带状疱疹后遗神经痛 

分 类 号：R246.7[医药卫生—针灸推拿学] R752.12[医药卫生—中医临床基础]