母婴分离对子代大鼠海马Wnt信号分子的影响  

Effects of maternal and infant separation on Wnt signaling molecules in hippocampus of offspring rats

作　　者：张玉荣[1] 王瑞忠 王莉[1] 赵丽丽 陈琳[3] 陈蕊[4] ZHANG Yurong;WANG Ruizhong;WANG Li;ZHAO Lili;CHEN Lin;CHEN Rui(Department of Scientific Research Affairs,First Affiliated Hospital of Xi’an Medical University,Xi’an,Shaanxi Province,710077;Pharmaceutical Preparation Center,Xi’an Daxing Hospital,Xi’an,Shaanxi Province,710077,China;Department of Pharmacy,First Affiliated Hospital of Xi’an Medical University,Xi’an,Shaanxi Province,710077;Department of Gynecology,First Affiliated Hospital of Xi’an Medical University,Xi’an,Shaanxi Province,710077)

机构地区：[1]西安医学院第一附属医院科研科,西安710077 [2]西安大兴医院制剂中心,西安710077 [3]西安医学院第一附属医院药学部,西安710077 [4]西安医学院第一附属医院妇科,西安710077

出　　处：《第三军医大学学报》2021年第20期2167-2172,共6页Journal of Third Military Medical University

基　　金：西安市科技计划项目[2019114613YX001SF040(7)]。

摘　　要：目的探索母婴分离(maternal and infant separation,MS)对子代大鼠焦虑和抑郁样行为、海马Wnt信号分子及其受体的影响。方法将体质量240~260 g的16只SD母鼠分为2组:对照组(CON,n=8)在产后不进行任何处理。母婴分离组(MS,n=8)在正常分娩后给予母婴分离应激,母鼠与子代大鼠每天分离3 h,连续14 d。采用高架十字迷宫实验(elevated plus maze test,EPMT)及强迫游泳实验(forced swimming test,FST)评估1月龄子代大鼠的焦虑样和抑郁样行为。采用实时定量PCR检测海马中Wnt分子的变化,通过Western blot测定大鼠海马Wnt2和Wnt3a蛋白的表达及Wnt信号通路抑制分子DKK1和sFRP3的表达。结果与CON组相比,MS组的子代大鼠高架十字迷宫实验中入臂总次数(OAE+CAE)差异无统计学意义,进入开放臂次数百分比显著降低(P<0.01),开放臂滞留时间百分比显著降低(P<0.05);MS组子代大鼠的不动时间显著延长(P<0.05),子代大鼠产生明显的焦虑、抑郁样行为。MS组子代大鼠海马Wnt2和Wnt3a的mRNA表达水平显著降低(P<0.01)。同时,MS组子代大鼠海马DKK1和sFRP3表达水平显著升高(P<0.01)。结论母婴分离导致子代大鼠产生抑郁和焦虑样行为,可能与海马Wnt信号分子紊乱相关。Objective To determine the effects of maternal and infant separation(MS)on anxiety and depression-like behaviors,Wnt signaling molecules and receptors in the hippocampus of offspring rats.Methods Sixteen Sprague-Dawley(SD)pregnant rats(240~260 g)were randomly and equally divided into 2 groups.The offspring rats from the control group(CON)received no postpartum intervention,while those of the experiment group(MS)were given maternal-infant separation 3 h per day for 14 consecutive days since delivery.Elevated plus maze test(EPMT)and forced swimming test(FST)were conducted to evaluate the anxiety and depression-like behaviors of 1-month-old offspring rats.Real-time quantitative PCR was used to detect the levels of Wnt molecules in the hippocampus of the offspring rats,and Western blotting was adopted to determine the expression of Wnt2 and Wnt3 a proteins as well as the Wnt signaling pathway inhibitory molecules DKK1 and sFRP3 in the hippocampus.Results The total number of arm entries(including open-arm and close-arm entries)was not statistically different between the MS and CON groups.However,the MS group had significantly lower percentages of open-arm entries(P<0.01)and open-arm time(P<0.05),and longer stationary time(P<0.05)in the FST than the CON group,indicating obvious anxiety and depression-like behaviors.Moreover,the mRNA levels of Wnt2 and Wnt3 a in the hippocampus were notably decreased(P<0.01),while the protein levels of DKK1 and sFRP3 were increased remarkably(P<0.01)in the MS group than the CON group.Conclusion Maternal and infant separation leads to depression and anxiety-like behaviors in offspring rats,which may be associated to the disorder of Wnt signaling molecules in the hippocampus.

关 键 词：母婴分离 Wnt信号分子 抑郁 海马 抑制分子 

分 类 号：R363.15[医药卫生—病理学] R363.21[医药卫生—基础医学]