针刺调控海马NRG3/ErbB4通路对尼古丁成瘾大鼠戒断症状的影响  

Effects of acupuncture on withdrawal symptoms in nicotine-addicted rats via regulation of the hippocampal NRG3/ErbB4 pathway

作　　者：张菀桐 朱宝琛 杨金生[3] 王莹莹[4] 刘朝[5] ZHANG Wantong;ZHU Baochen;YANG Jinsheng;WANG Yingying;LIU Zhao(Institute of Clinical Pharmacology,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100029,China;Department of Pharmacy,Dongzhimen Hospital,Beijing University of Chinese Medicine,Bejing 100700,China;Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Institute of Acupuncture and Moxibustion,China Academy of Chinese Medical Sciences,Beijing 100700,China;Department of Tobacco Control and Respiratory Disease Prevention,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]中国中医科学院西苑医院临床药理研究所,北京100091 [2]北京中医药大学东直门医院药学部,北京100700 [3]中国中医科学院中医基础理论研究所,北京100700 [4]中国中医科学院针灸研究所,北京100700 [5]中日友好医院控制吸烟与呼吸疾病防控部,北京100029

出　　处：《中华中医药杂志》2025年第2期550-556,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：中国医学科学院呼吸病学研究院青年科学基金项目(No.2023-ZF-65);国家中医药管理局中医药传承与创新“百千万”人才工程2022年青年岐黄学者培养项目,首都卫生发展基金自主创新项目(No.首发2024-2-4372);国家中医药管理局青年岐黄专项基金项目(No.11055);中国中医科学院科技创新工程(No.CI2021A03506)。

摘　　要：目的:观察针刺调控海马神经调节蛋白3(NRG3)/人表皮生长因子受体(ErbB4)通路对尼古丁成瘾大鼠戒断症状的影响。方法:48只SD大鼠随机分为空白对照组、模型组、假针刺组和针刺组,每组12只。模型组、假针刺组和针刺组使用尼古丁烟雾暴露的方法制备尼古丁成瘾模型。成功造模后,针刺组给予针刺“百会”“三阴交”和“足三里”穴,每次20 min;假针刺组仅给予浅刺,每次10 min;两组均为每日1次,共干预28 d。检测大鼠体质量、观察出现的戒断症状;尼氏染色和FJB染色观察大鼠海马组织病理变化情况;羟胺法检测海马组织中超氧化物歧化酶(SOD)活力;硫代巴比妥酸法检测海马组织中丙二醛(MDA)水平;酶联免疫吸附法检测海马组织中白细胞介素6(IL-6)、白细胞介素1β(IL-1β)及肿瘤坏死因子α(TNF-α)水平;Western Blot和实时荧光定量PCR分别检测海马组织中NRG3、ErbB4、PI3K、AKT、RAS、ERK蛋白及mRNA的表达。结果:模型组大鼠出现明显戒断症状,针刺组大鼠戒断症状明显缓解,且戒断症状评分显著低于模型组和假针刺组(P<0.05)。与空白对照组比较,模型组大鼠海马组织尼氏小体数量明显减少,神经元细胞体积缩小,形态不规则,排列紊乱,FJB阳性细胞明显增多;与模型组比较,假针刺组、针刺组大鼠海马组织神经元细胞损伤减轻,排列趋于整齐,FJB阳性细胞明显减少。与模型组比较,假针刺组、针刺组海马组织SOD活性显著升高(P<0.05),MDA水平显著降低(P<0.05),IL-6、IL-1β及TNF-α水平显著降低(P<0.05),针刺组大鼠海马NRG3和ErbB4蛋白及mRNA表达显著降低(P<0.05),PI3K、AKT、RAS、ERK蛋白及mRNA表达显著升高(P<0.05)。结论:针刺可有效缓解尼古丁成瘾大鼠的戒断症状,其中枢作用机制可能与提高海马组织中SOD的活性,降低MDA水平、减少炎症因子的释放及调节海马组织中NRG3、ErbB4蛋白和mRNA表达水平相关。Objective:To observe the effects of acupuncture on withdrawal symptoms in nicotine-addicted rats via regulation of the hippocampal NRG3/ErbB4 pathway.Methods:Forty-eight SD rats were randomly divided into a blank control group,a model group,a sham acupuncture group and an acupuncture group,with 12 rats in each group.Nicotine-addicted models were established in the model,acupuncture,and sham acupuncture groups through nicotine smoke exposure.After successful modeling,the acupuncture group received acupuncture at the‘Baihui(DU 20)',‘Sanyinjiao(SP 6)',and Zusanli(ST 36)'points,20 min per session.The sham acupuncture group received shallow needling at the same points without stimulation,10 minutes each time.Both the acupuncture treatment was given once daily for 28 days.once daily for 28 days.After the intervention,the body weight of the rats was measured,and withdrawal symptoms were observed.The pathological changes in the hippocampal tissue were observed by using Nissl staining and FJB staining.Superoxide dismutase(SOD)activity in the hippocampal tissue was measured by the hydroxylamine method,and malondialdehyde(MDA)levels were assessed by the thiobarbituric acid method.Levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-a)were determined by enzyme-linked immunosorbent assay(ELISA).The protein and mRNA expressions of NRG3,ErbB4,PI3K,AKT,RAS,and ERK in the hippocampal tissue were detected by Western Blot and real-time quantitative PCR.Results:Rats in the model group exhibited significant withdrawal symptoms,which were notably alleviated in the acupuncture group.The withdrawal symptom scores in the acupuncture group were significantly lower than those in the model group and the sham acupuncture group(P<0.05).Compared to the normal group,rats in the model group showed a marked decrease in the number of Nissl bodies in the hippocampal tissue,reduced neuronal cell body volume,rregular morphology,disordered arrangement,and a significant increase in FJB-positive cells.Compared to th

关 键 词：针刺 尼古丁成瘾 戒断症状 海马组织 NRG3/ErbB4通路 

分 类 号：R245[医药卫生—针灸推拿学]