摘要
目的 探讨腕踝针是否通过调控脊髓背角小胶质细胞α7nAChR影响JAK2/STAT3通路,缓解化疗所致神经性疼痛。方法 构建小胶质细胞特异性α7nAChR敲除小鼠(。将其与同窝α7nAChR^(flox/flox)小鼠分为对照组、模型组、腕踝针组及腕踝针+敲除组。紫杉醇腹腔注射制备疼痛模型。腕踝针组及腕踝针+敲除组予电针干预。检测机械痛阈(PWT)与热痛潜伏期(PWL);免疫荧光检测α7nAChR及Iba-1;Western blot检测p-JAK2/JAK2、p-STAT3/STAT3;RT-qPCR检测IL-1β、IL-6、TNF-α mRNA。结果 模型组PWT、PWL显著低于对照组(P<0.001),α7nAChR表达降低,Iba-1、p-JAK2/JAK2、p-STAT3/STAT3及炎症因子升高(P<0.001);腕踝针可改善上述变化(P<0.01或P<0.001),而敲除α7nAChR后该改善作用减弱(P<0.01或P<0.001)。结论 腕踝针可能通过上调脊髓背角小胶质细胞α7nAChR,抑制JAK2/STAT3磷酸化,减轻炎症反应,缓解化疗所致神经性疼痛。
Objective To investigate whether wrist-ankle acupuncture alleviates chemotherapy-induced neuropathic pain by regulating microglialα7nAChR in the spinal dorsal horn to influence the JAK2/STAT3 pathway.Methods Microglia-specificα7nAChR knockout mice(α7nAChRflox/flox;Cx3Cr1-Cre/ERT2)were generated.These mice,along with their littermateα7nAChRflox/flox mice,were divided into the following groups:control group,model group,wrist-ankle acupuncture group,and wrist-ankle acupuncture+knockout group.A paclitaxel-induced pain model was established via intraperitoneal injection.The wrist-ankle acupuncture group and wrist-ankle acupuncture+knockout group received electroacupuncture intervention.Mechanical pain threshold(PWT)and thermal pain latency(PWL)were assessed.Immunofluorescence was used to detectα7nAChR and Iba-1 expression.Western blot was performed to measure the ratios of p-JAK2/JAK2 and p-STAT3/STAT3.RT-qPCR was used to detect mRNA levels of IL-1β,IL-6,and TNF-α.Results Compared with the control group,the model group showed significantly lower PWT and PWL(P<0.001),reducedα7nAChR expression,and elevated levels of Iba-1,p-JAK2/JAK2,p-STAT3/STAT3,and inflammatory cytokines(P<0.001).Wrist-ankle acupuncture ameliorated these changes(P<0.01 or P<0.001),whereas the therapeutic effect was attenuated followingα7nAChR knockout(P<0.01 or P<0.001).Conclusion Wrist-ankle acupuncture may alleviate chemotherapy-induced neuropathic pain by upregulatingα7nAChR expression in spinal dorsal horn microglia,thereby inhibiting JAK2/STAT3 phosphorylation and attenuating the inflammatory response.
作者
陈泓霖
庞莉娜
王惠琳
林壮举
俞向梅
王志福
CHEN Honglin;PANG Lina;WANG Huilin;LIN Zhuangju;YU Xiangmei;WANG Zhifu(College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,350122,China;College of Acupuncture and Tuina,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China;College of Acupuncture and Tuina,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;College of Integrated Traditional Chinese and Western Medicine&Academy of Integrated Traditional Chinese and Western Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350004,China;Guoyitang,Fujian University of Traditional Chinese Medicine,Fuzhou 350003,China)
出处
《时珍国医国药》
北大核心
2026年第6期1176-1182,共7页
JOURNAL OF LI-SHIZHEN TRADITIONAL CHINESE MEDICINE
基金
国家自然科学基金面上项目(82274658)
福建省自然科学基金(2023J01333)
针灸学科开放课题(XZJ2024002)
“十四五”国家中医药管理局中医康复学科开放课题(X2023010)
福建省大学生创新创业训练计划项目(202410393008)。
