下丘脑兴奋潜能增加介导孕期摄食限制所致子代雌性大鼠HPA轴高敏感性宫内编程  

Prenatal Food Restriction Programed the Hypersensitivity of the HPA Axis in Female Offspring Rats Through Stimulating the Hypothalamic Irritability

作　　者：蒋涛[1,2] 文印宪[3] 程思源[2] 徐丹[1,4] 汪晖[1,4] 

机构地区：[1]武汉大学基础医学院药理学系,湖北武汉430071 [2]湖北省随州市妇幼保健院/随州市儿童医院,湖北随州441300 [3]武汉大学中南医院骨科,湖北武汉430071 [4]发育源性疾病湖北省重点实验室,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2016年第3期345-349,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金重点项目(编号:81430089);重大合作项目(编号:81220108026)

摘　　要：目的:探讨下丘脑局部兴奋性在孕期摄食限制(PFR)所致子代雌性大鼠下丘脑-垂体-肾上腺(HPA)轴高应激敏感性编程中的作用。方法:建立大鼠PFR模型,孕20d处死部分母鼠取胎鼠。余自然生产,断奶后给予持续高脂饮食饲养,17周时处死一半动物。余于17-20周持续给予不可预测性慢性刺激(UCS)后处死。取雌性动物血清和下丘脑,检测相关指标。结果:PFR组下丘脑超微结构出现损伤,AVP、GAD65、vGLUT2mRNA水平降低,vGLUT2/GAD65比值升高(P<0.05)。UCS前,PFR组血清ACTH浓度、下丘脑CRH mRNA水平降低,vGLUT2/GAD65比值升高(P<0.05)。UCS后,PFR组血清ACTH增长率及下丘脑AVP mRNA水平、vGLUT2/GAD65比值均高于对照组(P<0.05)。结论:PFR诱导的宫内下丘脑局部高兴奋性参与了子代雌性大鼠成年后HPA轴高应激敏感性编程。Objective：To investigate the role of hypothalamic irritability induced by the prenatal food restriction（PFR）in the stimulated sensitivity of the hypothalamic-pituitary-adrenal（HPA）axis in female offspring rats.Methods：PFR model was established by reducing 50%food administration of the pregnant rats since pregnant day 11.Then,the rats were killed under anaesthesia at pregnant day 20.The left pregnant rats were kept until spontaneous labor.All the female offspring were fed with high fat diet.Then,half of the rats were killed,while the left were underwent unpredictable chronic stresses（UCS）from postnatal week 17 to 20and killed as well.The bloodand hypothalamus were collected.Serum adrenocorticotropic hormone（ACTH）,hypothalamic mRNA level of hypothalamus corticotrophin-releasing hormone（CRH）,arginine vasopressin（AVP）,vesicular glutamate transporter 2（VGluT2）,glutamic acid decarboxylase 65（GAD65）,and ultrastructure of fetal hypothalamus were detected.Results：Abnormal changes in ultrastructure were observed in fetal hypothalamus.The mRNA levels of AVP,GAD65,vGLUT2 were decreased,while the vGLUT2/GAD65 ratio was increased.Before UCS,lower ACTH serum concentration and CRH mRNA level,as well as increased vGLUT2/GAD65 ratio,were detected in PFR group.Then,the rate of the serum ACTH rise,the AVP mRNA level and vGLUT2/GAD65 ratio were elevated after UCS.Conclusion：PFR stimulated the sensitivity of the HPA axis in female offspring rats through boosting the hypothalamic irritability.

关 键 词：孕期摄食限制 下丘脑 下丘脑-垂体-肾上腺轴 高应激敏感性 宫内编程 

分 类 号：R715.3[医药卫生—妇产科学]