CRH介导妊娠期慢性应激致子代雄鼠抑郁  

CRH mediate chronic pregnacy stress inducing depression in offspring male mice

作　　者：况亮[1] 吕逸丽 韩振敏 陈鹏 姚余有 唐伟 Kuang Liang;Lu Yili;Han Zhenmin(Dept of Nutrition and Food Hygiene,School of Public Health,Anhui Medical University,Hefei 23003)

机构地区：[1]安徽医科大学公共卫生学院营养与食品卫生学系,合肥230032 [2]安徽医科大学公共卫生学院人口健康与优生安徽省重点实验室,合肥230032 [3]安徽医科大学第二附属医院检验科,合肥230601

出　　处：《安徽医科大学学报》2018年第4期584-588,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽高校省级自然科学研究重点项目(编号:KJ2016A354)

摘　　要：目的探讨促肾上腺皮质激素释放激素(CRH)是否介导妊娠期慢性应激致子代抑郁及其可能机制。方法实验分为正常对照组(Control组)、产前应激+溶剂对照组(CPS组)、产前应激+CRHR1拮抗剂组(CPS+ANT组)。应用强迫游泳实验、糖水偏好实验和旷场实验对子代雄鼠的抑郁程度进行检测。应用HE染色法观察小鼠海马CA3区神经元的组织病理形态。Western blot法检测子代雄鼠海马组织雷帕霉素靶蛋白(m TOR)的表达量,运用ELISA法检测子代雄鼠海马CRH水平。结果与Control组相比,CPS组强迫游泳实验中小鼠不动时间增多(P<0.05);糖水偏好实验中糖水偏好率下降(P<0.05);旷场实验中站立次数、平均速度、穿越格子次数、鼠爬行总路程减少(P<0.05);海马CA3区神经元细胞数目较少,脱失现象明显,排列疏松紊乱,核浓染固缩;海马组织m TOR的表达量减少(P<0.05);海2017-12-14接收马CRH浓度升高(P<0.05)。与CPS组相比,CPS+ANT组强迫游泳实验中小鼠不动时间减少(P<0.05);糖水偏好率增高(P<0.05);旷场实验中鼠爬行总路程、平均速度、穿越象限次数、站立次数增加(P<0.05);海马CA3区神经元细胞数目较多,脱失现象明显减少,核固缩浓染减少;海马组织m TOR的表达量增多(P<0.05);海马CRH浓度下降(P<0.05)。结论 CRH介导了妊娠期慢性应激致子代抑郁,其机制可能与妊娠期慢性应激致子代海马CRH升高,下调m TOR蛋白表达,同时与CA3区神经元的减少有关。Objective To explore whether the corticotropin-releasing hormone（ CRH） mediate offspring depression induced by chronic pregnacy stress,and the possible mechanism. Methods Male offspring were randomly divided into the control group（ Control group）,the chronic prenatal stress group（ CPS group）,and the chronic prenatal stress ＋ CRHR1 antagonist group（ CPS ＋ ANT group）. Offspring male mice depression was investigated by the open field test,sucrose preference test,and forced swimming test,and the light microscope was used to examine the histopathologic changes in CA3 field of the hippocampus. In addition,Western blot was used to observe the expression of m TOR in hippocampus. Furthermore,ELISA was used to examine the hippocampus levels of CRH in the offspring mice. Results The CPS group offspring mice had less motion time compared with the Control group（ P〈 0. 05）. The sugar preference rate was decreased in the sugar preference test（ P 〈0. 05）. In the open field test,the distance,the mean speed,the number of line crossings and the number of standing times were decreased（ P 〈0. 05）,and the neuropathological changes were characterized by the soma condensation,loosed neurons,decreased neuron number,nuclear pyknosis in the CA3 field of hippocampus. Moreover,the expression of m TOR were decreased in hippocampus,and the hippocampus CRH concentration were increased（ P〈 0. 05）. Compared with the CPS group,the offspring mice had more motion time in CPS ＋ ANT group（ P 〈0. 05）. The sugar preference rate was increased in the sugar preference test（ P〈 0. 05）. In the open field test,the distance,the mean speed,the number of line crossings and the number of standing times were increased（ P 0. 05）,and the neuropathological changes were characterized by the increased neuron number,decresed number of damaged neuron in the CA3 field of hippocampus. The expression of m TOR were increased in hippocampus,and the hippocampus CRH concentration were decreased（ P〈 0. 05）. Conc

关 键 词：妊娠期慢性应激 促肾上腺皮质激素释放激素 CRHR1拮抗剂 抑郁 

分 类 号：R749.42[医药卫生—神经病学与精神病学]