雌激素对雌性小鼠社会行为及脑内催产素系统的调节作用  

Effects of Estrogen on Social Behavior and Oxytocin System in Brain of Female Mice

作　　者：付温爽 徐桂萍 郑嘉琪 傅筱 徐晓虹[1] FU Wen-shuang;XU Gui-ping;ZHENG Jia-qi;FU Xiao;XU Xiao-hong(Key Laboratory of Wildlife Biotechnology and Conservation and Utilization of Zhejiang Province,College of Chemistry and Life Sciences,Zhejiang Normal University,Jinhua 321004,China)

机构地区：[1]浙江师范大学化学与生命科学学院,浙江省野生动物生物技术与保护利用重点实验室,浙江金华321004

出　　处：《中国药学杂志》2023年第5期410-418,共9页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金面上项目资助(22176178,81773392);浙江省自然科学基金面上项目资助(LY20H260003)。

摘　　要：目的研究雌激素对雌鼠社会行为的影响及其机制。方法建立青春期去卵巢(OVX)小鼠模型,分为正常对照、假手术、OVX、OVX给予苯甲酸雌二醇(estradiol benzoate,EB,10、50μg·kg^(-1)·d^(-1))补充组,OVX造模后1周给予EB处理,直至实验结束(第6~13周龄)。小鼠成年后,检测其社会行为,ELISA分析血清和脑内17β-雌二醇(17β-E2)水平,免疫荧光和免疫组化分析下丘脑多个脑区和内侧杏仁核(MeA)的催产素免疫阳性(oxytocin immunoreactive,OT-ir)和OT受体免疫阳性(OTR-ir)神经元数目,并Western blot分析其雌激素α和β受体(ERα/β)表达水平。结果生理剂量EB补充能逆转OVX雌鼠和异性社交、接受性行为、母性育婴等社会行为的减弱,提高其受损的社会识别能力,恢复OVX雌鼠相关脑区减少的OT-ir和OTR-ir神经元数目及下调的17β-E2水平和ERα/β表达并存在脑区差异。结论雌激素可促进雌鼠对异性的社会交互和接受性行为、母性育婴等社会行为,这可能与其上调相关脑区ERα/β表达并增强这些脑区OT系统活动而提高社会识别能力有关。OBJECTIVE To study the effects of estrogen on social behavior of female mice and underlying mechanisms.METHODS After sham or ovariectomy(OVX)underanesthesia,pubertal(4-week-old)ICR female mice were divided into normal control(Con),sham operation(Sham),OVX,and OVX with estradiol benzoate(EB,10,50μg·kg^(-1).d^(-1))supplementation(OVX+EB)groups,EB supplementation was continued until the end of the experiment.At adult(13-week-old),social behaviors were tested.The level of 17β-estradiol(17β-E2)in serum and the brain was analyzed by ELISA.The numbers of OT-iror OTR-ir neurons in multiple brain regions of hypothalamus and medial amygdala(MeA)were analyzed by immunofluorescence or immunohis-tochemistry respectively,and estrogen receptorαandβ(ERa/β)levels in these brain areas were analyzed by Western blot.RESULTS EB supplementation at physiological doses reversed the inhibitionin social behaviors of OVX female mice,such as social interaction with male and accepting male sexuality,maternal rearing,and social recognition ability,restored the reduction of OT-ir and OTR-ir neurons in the hypothalamus and MeA of OVX female mice,increased the level of 17-E2 in serum and the brain,and upregulated the expressions of ERa/βin the MeA and ERβin the hypothalamus of OVX mice.CONCLUSION Estrogen promotes social interaction,accepting male sexuality and maternal rearing of female mice,which may be related to the up-regulation of the expression of ERa/βin related brain regions to social behavior and the enhancement of OT system activity and thusimprove-ment in social recognition.

关 键 词：雌激素 社会行为 下丘脑 杏仁核 催产素 

分 类 号：R966[医药卫生—药理学]