阿米替林对CCD诱发疼痛模型大鼠海马NMDA受体NR2B亚基表达和空间记忆的影响  

Effects of Amitriptyline on NR2B Subunit of NMDA Receptor Expression in the Hippocampus of Pain Model induced by CCD and Spatial Memory

作　　者：杨舟静 于剑锋[1] 陈静[1] 高文洁[1] 王孟岩[1] 王钢[2] 

机构地区：[1]潍坊医学院麻醉学系,山东潍坊261053 [2]潍坊医学院认知神经科学实验室

出　　处：《潍坊医学院学报》2017年第4期241-244,301,共5页Acta Academiae Medicinae Weifang

基　　金：国家自然科学基金资助课题(课题编号:81241041);山东省自然科学基金资助课题(课题编号:ZR2012HM077);潍坊医学院前沿探索重点研究基金课题(课题编号:K11TS1002);潍坊医学院大学生科技创新基金课题(课题编号:KX2016017)

摘　　要：目的探讨阿米替林(AMI)对神经病理性疼痛大鼠认知和海马N-甲基-D-天门冬氨酸(NMDA)受体NR2B亚基表达的影响。方法将32只体重250~300g雄性Wistar大鼠随机分为4组(n=8):假手术腹腔注射生理盐水组(SO+NS组),假手术腹腔注射AMI组(SO+AMI组),背根神经节压迫(CCD)模型腹腔注射生理盐水组(CCD+NS组),CCD模型腹腔注射AMI组(CCD+AMI组)。采用CCD的方法制备神经病理性疼痛模型。CCD后5d开始腹腔每天注射AMI 10mg/kg或同体积生理盐水。各组大鼠分别于术后3,7,14,21,28d测右侧后爪机械缩足阈值。术后第28~32天,八臂迷宫检测大鼠的认知功能,检测后立即处死大鼠以蛋白印迹和反转录PCR方法检测大鼠对侧海马NR2B mRNA和蛋白表达水平。结果与SO+NS比较,CCD+NS组痛阈降低,出现空间记忆降低,对侧海马NR2B mRNA和NR2B蛋白表达明显减少。与CCD+NS组比较,CCD+AMI组空间记忆明显改善,NR2B mRNA和蛋白的表达明显增加。结论 AMI可部分反转神经病理性疼痛导致的空间记忆功能障碍并使海马的NR2B表达上调。Objective To investigate amitriptyline（ AMI） alters cognitive dysfunction and expression level of NR2B subunit in the hippocampus in a rat. Methods Rats were randomly divided into four groups（ n = 8 per group）,including 2 sham operation groups,which were treated by normal saline（ Sham ＋ NS group） or AMI（ Sham ＋ AMI group）,other 2 groups with chronic compression of DRG,a normal saline-treated CCD group（ CCD ＋ NS group）,and a AMI-treated CCD group（ CCD ＋ AMI group）. A rat model of neuropathic pain was induced by compression the right L4 and L5 dorsal root ganglion. After the model was successfully established 5-（th）day,SO ＋ AMI group and CCD ＋ AMI group administration of intraperitoneal injection of AMI. And normal saline was administrated of intraperitoneal injection on SO＋ NS group and CCD ＋ NS group. Each group was evaluated using the mechanical withdrawal threshold（ MWT） at 3-（th）,7-（th）,14-（th）,21-（th）,28 -（th）days and the eight-arm radial maze task at 28-（th）day to 32-（th）day. The mRNA and protein levels of the NR2B in the contralateral hippocampus were measured by RT-PCR,western blot,and immunofluorescence on 28 day after CCD operation. Results Compared to SO ＋ NS group,the CCD ＋ NS group showed lower MWT,higher WME,RME and TE,lower mRNA and protein expression of NR2B in contralateral hippocampus. Compared to CCD ＋ NS group,the spatial memory of CCD ＋ AMI group was obviously improved,and the expression level of NR2B mRNA and protein were obviously increased. Conclusion AMI may partially reverse the spatial memory dysfunction induced by neuropathic pain,and up-regulate the expression of NR2B in the hippocampus.

关 键 词：阿米替林 神经病理性疼痛 空间记忆 海马 NR2B亚基 

分 类 号：R971.1[医药卫生—药品]