基于脊髓背角5-HT_(1A)R途径探讨腕踝针治疗紫杉醇诱导神经性疼痛小鼠的镇痛机制  

Exploration on the analgesic mechanism of wrist-ankle acupuncture in paclitaxelinduced neuropathic pain in mice via the spinal dorsal horn 5-HT_(1A)R pathway

作　　者：兰艳艳 庞莉娜 黄秋玲 王志福 LAN Yanyan;PANG Lina;HUANG Qiuling;WANG Zhifu(College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;The Affliated Rehabilitation Hospital,Fujian University of Traditional Chinese Medicine,Fuzhou 350003,China;College of Acupuncture and Moxibustion,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学康复医学院,福州350122 [2]福建中医药大学附属康复医院,福州350003 [3]福建中医药大学针灸推拿学院,福州350122

出　　处：《中华中医药杂志》2025年第3期1081-1085,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.82274658);福建省自然科学基金项目(No.2022J01347)。

摘　　要：目的:探讨腕踝针对紫杉醇诱导神经性疼痛(PINP)小鼠脊髓背角5-羟色胺_(1A)受体(5-HTIAR)、谷氨酸(Clu)、囊泡型谷氨酸转运体2(VGluT2)及p-CaMKI表达的影响,揭示其缓解化疗神经痛的机制。方法:将2月龄雄性C57BL/6小鼠48只随机分为对照组、模型组、腕踝针组、腕踝针+拮抗剂组,每组12只。模型组、腕踝针组及腕踝针+拮抗剂组通过腹腔注射紫杉醇(2mg/kg,隔天1次,共4次)建立PINP模型;对照组注射等量溶剂。腕踝针组在造模第1天起对双侧踝部“下4”“下5”区进行电刺激干预,隔日1次,每次30min,共7次。腕踝针+拮抗剂组在第3、7、14天额外鞘内注射5-HTiR拮抗剂(1mg/kg)。在造模第0、7、14天采用热刺痛仪检测热痛阈值(PWL);免疫荧光法检测脊髓背角5-HTAR表达;免疫印迹法检测脊髓背角5-HT_(1A)R、VGluT2及p-CaMKⅡ蛋白表达;ELISA法检测Glu含量。结果:与对照组比较,模型组小鼠PWL显著降低(P<0.01),脊髓背角5-HT_(1A)R、Glu、VGluT2及p-CaMKⅡ表达增高(P<0.01);与模型组比较,腕踝针组PWL显著增高(P<0.01),5-HTiaR表达显著升高(P<0.05),Clu及VGluT2含量显著减少(P<0.05),p-CaMKIⅡ表达显著降低(P<0.01);与腕踝针组比较,腕踝针+拮抗剂组PWL显著降低(P<0.01),Glu、VGluT2及p-CaMKⅡ表达显著升高(P<0.05,P<0.01)。结论:腕踝针可能通过上调5-HTiAR,降低VGluT2及p-CaMKⅡ表达,减少Glu含量,从而缓解PINP。Objective:To investigate the effects of wrist-ankle acupuncture(WAA)on the expression of 5-HT1R,Glu,VGluT2,and p-CaMKⅡin the spinal dorsal horn of mice with paclitaxel-induced neuropathic pain(PINP),revealing its mechanism in alleviating PINP.Methods:A total of 48 male C57BL/6 mice(2 months old)were randomly divided into control,PINP,WAA,and WAA+antagonist groups(n=12).The model,WAA,and WAA+antagonist groups were induced with PINP by intraperitoneal injection of paclitaxel(2 mg/kg)every other day for four injections,while the control group received an equal volume of solvent.The WAA group received electrical stimulation at the bilateral‘Lower 4'and‘Lower 5'zones of the ankle starting from day 1 post-modeling,with stimulation applied every other day for 30 min,totaling 7 sessions.The WAA+antagonist group additionally received intrathecal injections of the 5-HT/AR antagonist(1 mg/kg)on days 3,7,and 14.The thermal withdrawal latency(PWL)was measured on days O,7,and 14 post-modeling using a thermal pain threshold device.The expression of 5-HT1R in the spinal dorsal horn was assessed by immunofuorescence.The protein expression of 5-HT1R,VGluT2,CaMKⅡ,and p-CaMKⅡwas evaluated by Western blotting,and Glu levels were measured using ELISA.Results:Compared with the control group,PINP group showed a significant reduction in PWL(P<0.01)and an increase in the expression of 5-HT/AR,Glu,VGluT2,and p-CaMKⅡin the spinal dorsal horn(P<0.01).Compared with the PINP group,the WAA group demonstrated a significant increase in PWL(P<0.01),upregulation of 5-HTiAR(P<0.05),reduction in Glu and VGluT2 levels(P<0.05),and decreased p-CaMKⅡexpression(P<0.01).Compared with the WAA group,the WAA+antagonist group showed a decrease in PWL(P<0.01)and increased levels of Glu,VGluT2,and p-CaMKⅡ(P<0.05,P<0.01).Conclusion:WAA may alleviate PINP by upregulating 5-HT,AR,reducing VGluT2 and p-CaMKⅡexpression,and decreasing Glu levels.

关 键 词：紫杉醇诱导神经性疼痛 脊髓背角 5-羟色胺1A受体 腕踝针 中枢敏化 

分 类 号：R245[医药卫生—针灸推拿学]