塞来昔布对卒中后抑郁大鼠学习记忆能力及海马组织中脑源性神经营养因子表达的影响  

Effect of celecoxib on the learning and memory ability and the expression of brain-derived neurotrophic factor in hippocampus of rats with post-stroke depression

作　　者：武莉娜[1] 许国栋[2] 张雅安 宋景贵[4] 张朝辉[5] WU Li-na;XU Guo-dong;ZHANG Ya-an;SONG Jing-gui;ZHANG Zhao-hui(Department of Neurology,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Department of Neurosurgery,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Sanquan College,Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Department of Neurology,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China;Department of Psychiatry,the Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453002,Henan Province,China)

机构地区：[1]新乡医学院第三附属医院神经内科,河南新乡453003 [2]新乡医学院第三附属医院神经外科,河南新乡453003 [3]新乡医学院三全学院,河南新乡453003 [4]新乡医学院第一附属医院神经内科,河南卫辉453100 [5]新乡医学院第二附属医院精神科,河南新乡453002

出　　处：《新乡医学院学报》2019年第3期206-212,共7页Journal of Xinxiang Medical University

基　　金：国家自然科学基金资助项目(编号:81471349)

摘　　要：目的探讨塞来昔布对卒中后抑郁(PSD)大鼠学习记忆能力及海马组织中脑源性神经营养因子(BDNF)表达的影响。方法 60只Sprague-Dawley大鼠根据旷场实验(OFT)行为评分筛选50只行为评分均一的大鼠随机分为正常组、卒中组、抑郁组、PSD组、PSD干预组,每组10只。卒中组、PSD组和PSD干预组大鼠采用线栓法制备大脑中动脉阻塞(MCAO)模型;正常组及抑郁组大鼠给予假手术处理。抑郁组、PSD组和PSD干预组大鼠MCAO后给予孤养联合慢性不可预见性温和应激(CUMS)制备抑郁大鼠模型。PSD干预组大鼠于CUMS第1～29天给予塞来昔布25 mg·kg-1灌胃,每日2次;正常组、卒中组、抑郁组及PSD组大鼠分别给予等体积5 g·L-1羧甲基纤维素钠溶液灌胃。最终每组选择6只符合实验要求的大鼠。5组大鼠分别于MCAO前、MCAO后、CUMS后称体质量,并进行糖水消耗实验、OFT和被动规避实验。各组大鼠最后一次行为学评估后腹腔注射水合氯醛麻醉,快速断头处死,取脑组织,采用荧光定量聚合酶链反应和免疫组织化学技术检测大鼠海马组织中BDNF蛋白和mRNA的表达。结果MCAO前5组大鼠体质量比较差异均无统计学意义(P> 0. 05); MCAO后,卒中组、PSD组和PSD干预组大鼠体质量低于抑郁组和正常组(P <0. 05),卒中组、PSD组和PSD干预组大鼠体质量比较差异无统计学意义(P> 0. 05)。CUMS后,抑郁组、PSD组和PSD干预组大鼠体质量均低于正常组与卒中组(P <0. 05),PSD组大鼠体质量低于抑郁组(P <0. 05),PSD干预组大鼠体质量高于PSD组和抑郁组(P <0. 05)。MCAO前及MCAO后5组大鼠糖水偏好率比较差异均无统计学意义(P> 0. 05),抑郁组、PSD组及PSD干预组大鼠CUMS后糖水偏好率低于MCAO前和MCAO后(P <0. 05); CUMS后,抑郁组、PSD组及PSD干预组大鼠糖水偏好率均低于正常组和卒中组(P <0. 05),PSD组大鼠糖水偏好率低于抑郁组(P <0. 05),PSD干预组大鼠糖水偏好率高于PSD组�Objective To investigate the effect of celecoxib on the learning and memory ability and the expression of brain-derived neurotrophic factor( BDNF) in hippocampus of rats with post-stroke depression( PSD). Methods Fifty rats with uniform behavior score were screened from 60 Sprague-Dawley rats according to the open field test( OFT) behavior score,and the 50 rats were divided into normal group,stroke group,depression group,PSD group and PSD intervention group,10 rats in each group. The rat Models of middle cerebral artery occlusion( MCAO) were established by thread embolization in the stroke group,PSD group and PSD intervention group. The rats in the normal group and depression group were treated with sham operation. The rat in the depression group,PSD group and PSD intervention group were given solitary breeding combined with chronic unpredictable mild stress( CUMS) to prepare depression model after MCAO. The rats in the PSD intervention group were treated with celecoxib 25 mg·kg-1 by intragastric administration,twice a day from the first day to the twenty-ninth day during CUMS. The rats in the normal group,stroke group,depression group and PSD group were given the same volume of5 g·L-1 sodium carboxymethyl cellulose solution by intragastric administration. Finally,6 rats met the experimental requirements were selected in each group. The rats in the five groups were performed with weighing,sucrose consumption test,OFT and passive avoidance test at the time points of before MCAO,after MCAO and after CUMS,respectively. The rats in each group were anesthetized by intraperitoneal injection of chloral hydrate after the last behavior evaluation,and the rats were killed by rapid decapitation and the brain tissues were taken. The expression of BDNF mRNA and protein in hippocampus was detected by fluorescence quantitative polymerase chain reaction and immunohistochemistry. Results There was no significant difference in body mass of rats among the five groups before MCAO( P > 0. 05). After MCAO,the body mass of rats in th

关 键 词：塞来昔布 卒中后抑郁 学习记忆 脑源性神经营养因子 

分 类 号：R965[医药卫生—药理学]