母源性氟西汀暴露对雌性仔鼠慢性应激后下丘脑-垂体-肾上腺轴及学习记忆的影响  

Effects of maternal fluoxetine exposure on hypothalamic pituitary adrenal axis,as well as learning and memory function in female offspring rats after chronic stress

作　　者：张崇 潘洁 叶琳 李景[2] Zhang Chong;Pan Jie;Ye Lin;Li Jing(Department of Pharmacy,Xiangyang No.1 People's Hospital,Hubei University of Medicine,Xiangyang 441000,China;Department of Pharmacy,Renmin Hospital of Hubei Province,Medical College of Wuhan University,Wuhan 430070,China)

机构地区：[1]湖北医药学院附属襄阳市第一人民医院药学部,441000 [2]武汉大学人民医院药学部,430070

出　　处：《中华行为医学与脑科学杂志》2020年第1期2-7,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目(81703241)。

摘　　要：目的探讨母源性氟西汀暴露对雌性子代大鼠下丘脑垂体肾上腺(hypothalamic pituitary adrenal,HPA)轴及学习记忆功能的影响。方法孕鼠用随机数字表法分为处理组和对照组,分别于孕11~20 d给予10 mg/kg的氟西汀和等量的生理盐水。取两组的雌仔鼠各10只,于出生后12周分别行旷场实验、电迷宫实验和物体识别实验,测血浆促肾上腺皮质激素(adrenocorticotrophic hormone,ACTH)和皮质酮(corticosterone,CORT)浓度。然后给予21 d不可预见性慢性应激(Unpredictable chronic stress,UCS),并再次做上述实验。最后处死大鼠,取下丘脑组织,测定促肾上腺皮质激素释放激素(corticotropin releasing hormone,CRH)和精氨酸加压素(arginine vasopressin,AVP)的mRNA表达。采用SPSS 19.0进行描述和t检验。结果UCS前,两组大鼠的各检测指标均差异无统计学意义(均P>0.05)。UCS后,两组大鼠的水平运动、垂直运动较处理前均明显减少,且处理组大鼠的水平运动[(37.2±7.2)次,(50.8±8.5)次,t=4.73,P<0.01]和垂直运动[(10.6±2.0)次,(15.2±5.1)次,t=2.93,P<0.05]均低于对照组;两组大鼠的正确反应次数均明显减少,总反应时间明显延长;且处理组大鼠的正确反应次数明显少于对照组[(3.4±1.3)次,(4.5±0.9)次,t=2.36,P<0.05];处理组大鼠的物体辨别指数显著下降,且低于对照组[(0.11±0.04),(0.16±0.05),t=2.28,P<0.05]。UCS前后,处理组大鼠的ACTH变化率[(61.13±26.08)%,(29.83±12.73)%,t=3.67,P<0.01]和CORT变化率[(105.71±18.39)%,(74.15±39.24)%,t=2.34,P<0.05]均明显高于对照组,且下丘脑CRH的mRNA表达明显高于对照组(t=4.15,P<0.01)。结论未发现孕期氟西汀暴露对雌性子代大鼠HPA轴及学习记忆功能有明显的损害,但加重了慢性应激情况下HPA轴及学习记忆功能受损的易感性。Objective To investigate the effects of maternal fluoxetine exposure on hypothalamic pituitary adrenal(HPA)axis and learning and memory function in female offspring rats.Methods Pregnant rats were divided into treatment group and control group by a table of random numbers,which were given fluoxetine(10 mg/kg per day)or the same amount of normal saline at 11-20 days of gestation,respectively.Ten female offspring from each group were selected randomly for open field,electrical maze and object recognition tests at 12 weeks after birth,and the concentrations of serum adrenocorticotropic hormone(ACTH)and corticosterone(CORT)were determined.Then they were given an unpredictable chronic stress(UCS)for 21 days,and the previous experiments were repeated.Finally,rats were sacrificed and the hypothalamus tissues were taken to measure the mRNA expression of corticotropin releasing hormone(CRH)and arginine vasopressin(AVP).SPSS 19.0 was used for data describing and t-test.Results Before UCS,there were no significant differences between the two groups among all the indexes(all P>0.05).After UCS,the horizontal movement and vertical movement of the rats in the two groups were significantly reduced compared with that before treatment,and the horizontal movement of the rats in the treatment group((37.2±7.2)vs(50.8±8.5),t=4.73,P<0.01)and vertical movement((10.6±2.0)vs(15.2±5.1),t=2.93,P<0.05)were lower than those in the control group.The correct reaction times decreased and the total reaction time increased in the two groups.While the correct response times of the treatment group were significantly lower than that of the control group(3.4±1.5)vs(4.5±0.9),t=2.36,P<0.05).The object recognition index of the rats in the treatment group decreased significantly compared with the control group((0.11±0.04)vs(0.16±0.05),t=2.28,P<0.05).Before and after UCS,the change rate of ACTH((61.13±26.08)%vs(29.83±12.73)%,t=3.67,P<0.01)and CORT((105.71±18.39)%vs(74.15±39.24)%,t=2.34,P<0.05)in the treated group was significantly higher than t

关 键 词：氟西汀 学习记忆 下丘脑-垂体-肾上腺轴 慢性应激 

分 类 号：R28[医药卫生—中药学]