基于NRG1/ErbB4信号通路探讨针刺对孤独症谱系障碍行为学的影响  

Exploring the Effects of Acupuncture on Behaviors of Autism Spectrum Disorder Based on the NRG1/ErbB4 Signaling Pathway

作　　者：庄婉玉 洪钰[1] 张颖莹 陈思洁 黄龙生[1] 康洁 ZHUANG Wanyu;HONG Yu;ZHANG Yingying;CHEN Sijie;HUANG Longsheng;KANG Jie(Fujian Provincial Maternity and Child Health Care Hospital,Fuzhou,Fujian 350001,China;College of Traditional Chinese Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350122,China)

机构地区：[1]福建省妇幼保健院,福建福州350001 [2]福建中医药大学中医学院,福建福州350122

出　　处：《康复学报》2025年第1期44-50,共7页Rehabilitation Medicine

基　　金：国家自然科学基金项目(81804173);福建省自然科学基金项目(2022J01363);福建省科技创新联合资金项目(2020Y9145)。

摘　　要：目的 基于NRG1/ErbB4信号通路探讨针刺对孤独症谱系障碍(ASD)模型鼠行为活动的影响以及针刺改善ASD行为活动的可能机制。方法 采用成年SPF级Wistar大鼠,在雌鼠受孕12.5 d时采用腹腔注射丙戊酸钠的方法造模,取ASD模型鼠24只,采用随机数字表法分为模型组、针刺组和NRG1组,每组8只,其中NRG1组是在ASD模型基础上行侧脑室NRG1慢病毒感染后获得。针刺组取“智三针”穴位,针刺深度约1 mm,共留针40 min,每穴间隔10 min行针1次,模型组、NRG1组仅模拟抓取动作,以上3组干预均在每天同一时间进行,1次/d,连续干预14 d。采用三箱社交实验、旷场实验、Morris水迷宫观察大鼠行为活动,qPCR法和Western blot法分别检测大脑额叶NRG1、ErbB4 mRNA相对表达水平和蛋白相对表达量。结果在第一阶段中,与模型组比较,NRG1组接触陌生鼠1时间更长(P<0.05);与模型组比较,针刺组和NRG1组接触物体时间更短(P<0.05)。在第二阶段中,与模型组比较,针刺组和NRG1组接触陌生鼠1时间均更短(P<0.05);与模型组比较,针刺组和NRG1组接触陌生鼠2时间均更长(P<0.05)。与模型组比较,针刺组和NRG1组的探索行为即中间区域探索频次增多(P<0.05);与模型组比较,针刺组和NRG1组中间区域逗留时间增多(P<0.05)。在空间探索阶段,与模型组比较,NRG1组进入目标象限探索时间和穿越目标平台频次均明显增多(P<0.05);与模型组比较,针刺组和NRG1组游泳总距离明显减少(P<0.05)。与模型组比较,NRG1组NRG1、ErbB4 mRNA相对表达水平均升高(P<0.05)。与模型组比较,针刺组和NRG1组NRG1蛋白相对表达量均升高(P<0.05);与模型组比较,针刺组ErbB4蛋白相对表达量升高(P<0.05)。结论 针刺能够改善ASD行为活动,尤其是社会交往障碍这一核心症状,这可能与调控NRG1/ErbB4信号通路,促进NRG1和ErbB4表达有关。Objective To explore the effect of acupuncture on the behavioral activities of autism spectrum disorder(ASD)model rats based on the recombinant neuregulin 1/receptor protein-tyrosine kinase erbB-4 signaling pathway and to investigate the possible mechanism by which acupuncture improves the behavioral activities of ASD.Methods Adult SPF-grade Wistar rats were used.The model was established by intraperitoneal injection of sodium valproate in pregnant female rats at 12.5 days of gestation.Twenty-four ASD model rats were randomly divided into model group,acupuncture group,and NRG1 group,with 8 rats in each group.The NRG1 group was obtained by lateral ventricle NRG1 lentivirus infection on the basis of the ASD model.The acupuncture group was treated at the"Zhi San Zhen"acupoints,with a depth of approximately 1 mm,and the needles were retained for 40 minutes and manipulated once every 10 minutes at each acupoint.The model group and the NRG1 group only simulated the grasping action.The three groups were intervened at the same time every day,once a day,for 14 consecutive days.The behavioral activities of the rats were observed by the three-chamber social test,the open field test,and the Morris water maze.The relative mRNA and protein expression levels of NRG1 and ErbB4 in the frontal lobe of the brain were detected by qPCR and Western blot methods,respectively.Results In the first stage,compared with the model group,the NRG1 group spent more time in contact with the unfamiliar rat 1(P<0.05);compared with the model group,the acupuncture group and the NRG1 group spent less time in contact with the object(P<0.05).In the second stage,compared with the model group,the acupuncture group and the NRG1 group spent less time in contact with the unfamiliar rat 1(P<0.05);compared with the model group,the acupuncture group and the NRG1 group spent more time in contact with the unfamiliar rat 2(P<0.05).Compared with the model group,the exploration behavior,that is,the frequency of exploration in the middle area,increased in the acupun

关 键 词：孤独症谱系障碍 NRG1/ErbB4信号通路 针刺 社会交往障碍 行为学 

分 类 号：R245[医药卫生—针灸推拿学]