[1]武莉娜,许国栋,张雅安,等.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[J].新乡医学院学报,2019,36(3):206-212.[doi:10.7683/xxyxyxb.2019.03.002]
　WU Li-na,XU Guo-dong,ZHANG Ya-an,et al.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[J].Journal of Xinxiang Medical University,2019,36(3):206-212.[doi:10.7683/xxyxyxb.2019.03.002]
点击复制

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
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
36
期数:
2019年3
页码:
206-212
栏目:
基础研究
出版日期:
2019-03-05

文章信息/Info

Title:
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3; 宋景贵4; 张朝辉5
（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）
Author(s):
WU Li-na1; XU Guo-dong2; ZHANG Ya-an3; SONG Jing-gui4; ZHANG Zhao-hui5
(1.Department of Neurology,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003;2.Department of Neurosurgery,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003;3.Sanquan College,Xinxiang Medical University,Xinxiang 453003;4.Department of Neurology,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100;5.Department of Psychiatry,the Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453002)
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
Keywords:
celecoxib; post-stroke depression; learning and memory; brain-derived neurotrophic factor
分类号:
R971+.43R749.4
DOI:
10.7683/xxyxyxb.2019.03.002
文献标志码:
A
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组和抑郁组（P<0.05）。MCAO前及MCAO后5组大鼠水平运动得分、垂直运动得分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后水平运动得分、垂直运动得分低于MCAO前和MCAO后（P<0.05）；CUMS后，抑郁组、PSD组和PSD干预组大鼠水平运动得分、垂直运动得分均低于正常组与卒中组（P<0.05），PSD组大鼠水平运动得分、垂直运动得分低于抑郁组（P<0.05），PSD干预组大鼠水平运动得分、垂直运动得分高于PSD组与抑郁组（P<0.05）。MCAO前及MCAO后5组大鼠潜伏期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后潜伏期短于MCAO前和MCAO后（P<0.05）；CUMS后，抑郁组、PSD组和PSD干预组大鼠潜伏期短于正常组与卒中组（P<0.05），PSD组大鼠潜伏期短于抑郁组（P<0.05），PSD干预组大鼠潜伏期长于抑郁组和PSD组（P<0.05）。抑郁组、PSD组和PSD干预组大鼠海马组织中BDNF蛋白及mRNA相对表达量均低于正常组与卒中组（P<0.05），正常组与卒中组大鼠海马组织中BDNF蛋白及mRNA相对表达量比较差异无统计学差异（P>0.05），PSD干预组大鼠海马组织中BDNF蛋白及mRNA相对表达量高于抑郁组和PSD组（P<0.05），抑郁组与PSD组大鼠海马组织中BDNF蛋白及mRNA相对表达量比较差异无统计学差异（P>0.05）。结论　塞来昔布能改善PSD大鼠的抑郁行为及学习记忆能力，提高海马组织中BDNF蛋白和mRNA的表达。
Abstract:
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 of 5 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 the stroke group,PSD group and PSD intervention group was lower than that in the depression group and normal group (P<0.05),but there was no significant difference among the stroke group,PSD group and PSD intervention group (P>0.05).After CUMS,the body mass of rats in the depression group,PSD group and PSD intervention group was lower than that in the normal group and stroke group (P<0.05),the body mass of rats in the PSD group was lower than that in the depression group (P<0.05),and the body mass of rats in the PSD intervention group was higher than the body mass of rats in the PSD group and depression group (P<0.05).There was no significant difference in sugar preference rate among the five groups before and after MCAO (P>0.05).The sugar preference rate of rats after CUMS was lower than that before and after MCAO in the depression group,PSD group and PSD intervention group (P<0.05).After CUMS,the sugar preference rate of rat of rats in the depression group,PSD group and PSD intervention group was lower than that in the normal group and stroke group (P<0.05),the sugar preference rate of rats in the PSD intervention group was lower than that in the depression group (P<0.05),and the sugar preference rate of rats in the PSD intervention group was higher than that in the PSD group and depression group (P<0.05).There was no significant difference in the scores of horizontal and vertical movements of rats among the five groups before and after MCAO (P>0.05).The scores of horizontal and vertical movements of rats after CUMS were lower than those before and after MCAO in the depression group,PSD group and PSD intervention group (P<0.05).After CUMS,the scores of horizontal and vertical movements of rats in the depression group,PSD group and PSD intervention group were lower than those in the normal group and stroke group (P<0.05),while the scores in the PSD group were lower than those in the depression group (P<0.05),and the scores in the PSD intervention group were higher than those in the PSD group and depression group (P<0.05).There was no significant difference in the latency among the five groups before and after MCAO (P>0.05).The latency of rats after CUMS was shorter than that before and after MCAO in the depression group,PSD group and PSD intervention group (P<0.05).After CUMS,the latency of rats in the depression group,PSD group and PSD intervention group was shorter than that in the normal group and stroke group (P<0.05),the latency of rats in the PSD group was shorter than that inthe depression group (P<0.05),and the latency of rats in the PSD intervention group was longer than that in the depression group and PSD group (P<0.05).Conclusion　Celecoxib can improve the depressive behavior and learning and memory ability of PSD rats,and increase the expression of BDNF protein and mRNA in hippocampus.

参考文献/References:

［1］　李静，郑振雨，王静，等.卒中后抑郁患者载脂蛋白H与认知功能的相关性［J］.新乡医学院学报，2017，34（8）：719-722.
［2］　李强，陈敏，杨泰.抑郁症发病机制的研究进展［J］.神经疾病与精神卫生，2016，16（5）：524-527.
［3］　高之涵，金卫东.抗抑郁药物与抑郁症 HPA 轴功能关系的研究进展［J］.医药导报，2017，36（60）：659-664.
［4］　MAES M,GALECKI P,CHANG Y S,et al.A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness［J］.Prog Neuropsychophar-macol Biol Psychiatry,2011,35(3):676-692.
［5］　ZHANG Z H,WU L N,SONG J G,et al.Correlations between cognitive impairment and brain-derived neurotrophic factor expression in the hippocampus of post-stroke depression rats［J］.Mol Med Rep,2012,6(4):889-893.
［6］　LOUHINOUX I,KRONENBERG G,ENDRES M,et al.Post-stroke depression:mechanisms,translation and therapy［J］.J Cell Mol Med,2012,16(9):1961-1969.
［7］　TERRONI L,AMARO E,IOSIFESCN D V,et al,Stroke lesivn in cottical neural circuits and post-stroke incidence of major depressive episode：a 4-month prospective study［J］.World J Biol Psychiatry,2011,12(7):539-548.
［8］　HEIN M,ZOREMBA N,BLEILEVENS C,et al.Levosimendan limits reperfusion injury in a rat middle cerebral artery occlusion (MCAO) model［J］.BMC Neurol,2013,13(2)：106-112.
［9］　LI Y,YAN J,ZHU X,et al.Dilated Virchow-Robin spaces in the hippocampus impact behaviors and effects of anti-depressant treatment in model of depressed rats［J］.J Affect Disord,2017,219(1)：17-24.
［10］　LIU H,HUANG Q Y,SUN H Z,et al.Effects of separate or combined exposure of nonylphenol and octylphenol on central 5-HT system and related learning and memory in the rats［J］.Ecotoxicol Environm Saf,2019,172：523-529.
［11］　崔艳杰，孟智宏，张春红.中风后抑郁的中医药研究进展［J］.世界中医药，2017，12（10）:2527-2530.
［12］　LI W,LING S,YANG Y,et al.Systematic hypothesis for post-stroke depression caused inflammation and neurotransmission and resultant on possible treatments［J］.Neuro Endocrinol Lett,2014,35(2):104-109.
［13］　GUDASHEVA T A,POVARNINA P Y,SEREDENIN S B.Dipeptide mimetic of the brain-derived neurotrophic factor prevents impairments of neurogenesis in stressed mice［J］.Bull Exp Biol Med,2017,162(4):454-457.
［14］　CASTRN E,KOJIMA M.Brain-derived neurotrophic factor in mood disorders and antidepressant treatments［J］.Neurobiol Dis,2017,97(PtB):119-126.
［15］　GNTHER M,PLANTMAN S,DAVIDSSON J,et al.COX-2 regulation and TUNEL-positive eell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats［J］.Acta Neurochir,2015,157(4):649-659.
［16］　KAWAHARA K,HOHJOH H,INAZUMI T,et al.Prostaglandin E2-induced inflammation:relevance of prostaglandin E receptors［J］.Biochim Biophys Acta,2015,1851(4)：414-421.
［17］　SAINI S,LIU T,YOO J.TNF-α stimulates colonic myofibroblast migration via COX-2 and Hsp27［J］.J Surg Res,2016,204(1):145-152.
［18］　READER B F,JARRETT B L,MCKIM D B,et al.Peripheral and central effects of repeated social defeat stress：monocyte trafficking,microglial activation,and anxiety［J］.Neuroscience,2015,289(4):429-442.
［19］　KIM Y K,NA K S.Role of glutamate receptors and glial cells in the pathophysiology of treatment-resistant depression［J］.Prog Neuropsychopharmacol Biol Psychiatry,2016,70(2):117-126.
［20］　SB P,KALINICHENKO L,BAUM W,et al.Hippocampal structure and function are maintained despite severe innate peripheral inflannnation［J］.Brain Behav Immun,2015,49(2):156-170.
［21］　罗映.AA-COX2/5-LO信号通路参与抑郁大鼠学习记忆障碍机制及干预［D］.重庆：重庆医科大学，2015.
［22］　MORGESE M G,SCHIAVONE S,BOVE M,et al.Sub-chronic celecoxib prevents soluble beta amyloid-induced depressive-like behaviour in rats［J］.J Affect Disord,2018,238(2):118-121.
［23］　FOURRIER C,SAMPSON E,MILLS N T,et al.Anti-inflammatory treatment of depression:study protocol for a randomised controlled trial of vortioxetine augmented with celecoxib or placebo［J］.Trials,2018,19(1):282-290.

相似文献/References:

[1]籍玉红,宋景贵.交感神经皮肤反应在卒中后抑郁患者自主神经功能损害中的价值[J].新乡医学院学报,2008,25(01):040.
[2]宋景贵,穆俊林,张朝辉,等.卒中后抑郁和脑卒中患者血脂水平对照研究[J].新乡医学院学报,2010,27(01):042.
　SONG Jing-gui,MU Jun-lin,ZHANG Zhao-hui,et al.A control study of levels of serum lipid in patients with post-stroke depression and brain stroke[J].Journal of Xinxiang Medical University,2010,27(3):042.
[3]陈锦,孙彭利.塞来昔布诱导人肝癌细胞株QGY-7701 凋亡的研究[J].新乡医学院学报,2011,28(02):161.
[4]于红霞,张平,张朝辉,等.卒中后抑郁的功能性磁共振成像和结构性磁共振成像研究进展[J].新乡医学院学报,2022,39(12):1173.[doi:10.7683/xxyxyxb.2022.12.014]
　YU Hongxia,ZHANG Ping,ZHANG Zhaohui,et al.Research progress of post-stroke depression based on functional magnetic resonance imaging and structural magnetic resonance imaging[J].Journal of Xinxiang Medical University,2022,39(3):1173.[doi:10.7683/xxyxyxb.2022.12.014]
[5]张金培,范文涛.醒脑解郁方对卒中后抑郁大鼠海马组织中Notch/Hes信号通路功能的影响[J].新乡医学院学报,2017,34(11):965.[doi:10.7683/xxyxyxb.2017.11.003]
　ZHANG Jin-pei,FAN Wen-tao.Effect of Xingnao Jieyu Decoction on the function of Notch/Hes signaling pathway in hippocampus of rats with post-stroke depression[J].Journal of Xinxiang Medical University,2017,34(3):965.[doi:10.7683/xxyxyxb.2017.11.003]
[6]王旭生,张　萍,曾　皎,等.豫北地区急性脑梗死患者卒中后抑郁危险因素分析[J].新乡医学院学报,2020,37(5):484.[doi:10.7683/xxyxyxb.2020.05.020]
　WANG Xusheng,ZHANG Ping,ZENG Jiao,et al.Risk factors of post-stroke depression in patients with acute cerebral infarction in northern Henan province[J].Journal of Xinxiang Medical University,2020,37(3):484.[doi:10.7683/xxyxyxb.2020.05.020]
[7]张乾坤,王昊亮,许　帅,等.血清白细胞介素-2和白细胞介素-4水平与卒中后抑郁的相关性[J].新乡医学院学报,2019,36(1):028.[doi:10.7683/xxyxyxb.2019.01.006]
　ZHANG Qian-kun,WANG Hao-liang,XU Shuai,et al.Correlation between the levels of serum interleukin-2 and interleukin-4 and post stroke depression[J].Journal of Xinxiang Medical University,2019,36(3):028.[doi:10.7683/xxyxyxb.2019.01.006]
[8]石建伟.关节镜辅助下关节腔清理术治疗痛风性膝关节炎临床疗效及安全性[J].新乡医学院学报,2017,34(5):442.[doi:10.7683/xxyxyxb.2017.05.026]
　SHI Jian-wei.Curative effect and safety of arthroscopic debridement for treatment of gouty arthritis[J].Journal of Xinxiang Medical University,2017,34(3):442.[doi:10.7683/xxyxyxb.2017.05.026]
[9]李　静,郑振雨,王　静,等.卒中后抑郁患者载脂蛋白H与认知功能的相关性[J].新乡医学院学报,2017,34(8):719.[doi:10.7683/xxyxyxb.2017.08.015]
　LI Jing,ZHENG Zhen-yu,WANG Jing,et al.Correlation of apolipoprotein H and cognitive function in post-stroke depression patients[J].Journal of Xinxiang Medical University,2017,34(3):719.[doi:10.7683/xxyxyxb.2017.08.015]
[10]费鹏鸽,李智花,李文强,等.事件相关电位P300对脑卒中后抑郁患者认知功能障碍的评估价值[J].新乡医学院学报,2022,39(6):523.[doi:10.7683/xxyxyxb.2022.06.005]
　FEI Pengge,LI Zhihua,LI Wenqiang,et al.Value of event-related potential P300 in evaluating cognitive dysfunction of patients with post-stroke depression[J].Journal of Xinxiang Medical University,2022,39(3):523.[doi:10.7683/xxyxyxb.2022.06.005]

更新日期/Last Update: 2019-03-05