催产素减轻新生大鼠海马神经元缺氧缺血性损伤  

Role of oxytocin in neonatal rat hippocampal neurons after hypoxic-ischemic injury

作　　者：谢常宁 吴俭[1] 王欣萌 彭斯聪 吴静[1] 肖凌慧 柳涛[1,2,3] XIE Chang-ning;WU Jian;WANG Xin-meng;PENG Si-cong;WU Jing;XIAO Ling-hui;LIU Tao(Department of Pediatrics,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Center for Experimental Medicine,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China;Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China)

机构地区：[1]南昌大学第一附属医院儿科,江西南昌330006 [2]南昌大学第一附属医院医学科研中心,江西南昌330006 [3]南昌大学第一附属医院江西省分子诊断与精准医学重点实验室,江西南昌330006

出　　处：《中国病理生理杂志》2018年第4期739-744,753,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.31660289);江西省杰出青年人才资助计划(No.20171BCB23091);南昌大学研究生创新专项资金项目(No.cx2016318)

摘　　要：目的:探讨催产素(oxytocin)对新生大鼠缺氧缺血性损伤后海马CA1区神经元的作用及机制。方法:采用氧糖剥夺(OGD)制备体外缺氧缺血模型,取8只7~10日龄新生大鼠的急性分离脑片(6~8片/只)随机分为4组,即对照组、OGD 20 min组、OGD 40 min组和OGD+oxytocin组,进行TO-PRO-3染色实验观察催产素对神经元的作用。另取20只新生大鼠脑片随机分为4组,分别是OGD组、OGD+oxytocin组、OGD+d VOT(催产素受体阻断剂)+oxytocin组和OGD+bicuculline(GABAA受体阻断剂)+oxytocin组,用全细胞膜片钳记录不同药物作用下海马神经元缺氧去极化的出现时间。结果:TO-PRO-3染色结果显示海马CA1区神经元死亡数量随着氧糖剥夺时间延长而增加,催产素能显著减少OGD所致的死亡神经元数目(P<0.05)。全细胞膜片钳记录结果显示,催产素可使缺氧去极化时间显著延长;d VOT及bicuculline可以消除这种效应。结论:催产素能减轻新生大鼠海马CA1区神经元缺氧缺血性损伤,其机制可能是通过结合催产素受体,增强抑制性神经传递,从而产生神经保护作用。AIM:To investigate whether oxytocin has neuroprotective effects on hippocampal CA1 pyramidal neurons from neonatal rats exposed to hypoxic-ischemic brain injury and the underlying mechanisms.METHODS:An in vitro model of hypoxic-ischemic injury was used by exposing the brain slices to oxygen-glucose deprivation(OGD)solution.Acute dissociated brain slices(6~8 slices per rat)from 8 Sprague-Dawely rats of 7~10 d old were used.The slices were randomly divided into 4 groups:control group,OGD 20 min group,OGD 40 min group and OGD+oxytocin group.The effect of oxytocin on neuronal death was evaluated by TO-PRO-3 staining.Fresh brain slices from other 20 neonatal rats were divided into OGD group,OGD+oxytocin group,OGD+dVOT(oxytocin receptor antagonist)+oxytocin group,and OGD+bicucuclline(GABA A receptor antagonist)+oxytocin group.The onset of anoxic depolarization in the hippocampal neurons treated with different drugs was recorded by whole-cell patch-clamp techniques.RESULTS:The results of TO-PRO-3 staining showed that neuronal deaths in hippocampal CA1 area were increased over the prolonged OGD time.Oxytocin significantly reduced the hypoxic-ischemic deaths.Oxytocin dramatically prolonged the onset time of anoxic depolarization after the application of OGD solution.Both dVOT and bicuculline blocked this effect.CONCLUSION:Oxytocin plays a neuroprotective role in neonatal rat hippocampal CA1 pyramidal neurons by enhancing the inhibitory synaptic transmission via oxytocin receptors.Therefore,oxytocin is useful as a candidate for neuroprotective treatment after neonatal hypoxic-ischemic brain injury.

关 键 词：催产素 缺氧缺血性脑病 海马 膜片钳技术 

分 类 号：R722[医药卫生—儿科] R363[医药卫生—临床医学]