短期低剂量褪黑素与氯胺酮对慢性应激抑郁模型大鼠的抑郁样行为及BDNF表达的影响  

Effects of short term low dose melatonin and ketamine on depressive behavior and BDNF expressionin rats with chronic stress depression

作　　者：李浩男 孙宏伟[1] 王艳郁[1] 姜能志[1] 孙琳[1] 

机构地区：[1]潍坊医学院心理学系,潍坊261053

出　　处：《中华行为医学与脑科学杂志》2017年第12期1070-1075,共6页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：山东省优秀中青年科学家科研奖励基金计划项目（BS2014YY043）;山东省自然科学基金项目（ZR2014CL012）;山东省高等学校科技计划项目（J17KB096）;山东省自然科学青年基金项目（ZR2017QH001）;潍坊医学院教育教学改革与研究基金项目（2015Y024）

摘　　要：目的 探讨短期低剂量褪黑素与氯胺酮对慢性应激抑郁模型大鼠抑郁样行为及前额叶脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）和谷氨酸受体1（glutamate receptor 1, GluR1）免疫反应活性的影响.方法 40只两月龄Wistar雄性大鼠随机分成4组（n=10）：对照组（CON组）、慢性应激抑郁组（CUS组）、慢性应激抑郁＋褪黑素组（CUS＋MT组）和慢性应激抑郁＋氯胺酮组（CUS＋KET组）.除CON组外,余组大鼠接受42 d不同应激源暴露刺激.采用糖水偏好实验检测抑郁模型是否建立成功.CUS＋MT组大鼠予以褪黑素（10 mg/kg,i.g）灌胃给药,CUS＋KET组大鼠则腹腔注射氯胺酮（10 mg/kg,i.p）,药物处理均1次/d,给药14 d后进行强迫游泳实验并于实验开始后第58 d取处死大鼠,采用免疫组织化学法检测大鼠前额叶BDNF及GluR1免疫反应活性.结果 （1）与CON组相比,CUS组、CUS＋MT组和CUS＋KET组在建模后给药前出现明显抑郁样行为,糖水偏好比率下降（t=3.365,P〈0.05）,不动状态持续时间显著延长（P〈0.01）.（2）给药14 d后,与CUS组[（146.34±34.10）s]相比,CUS＋MT组[（60.70±18.56）s]与CUS＋KET组[（56.43±20.46）s]大鼠不动状态持续时间显著减少.CUS＋MT 组[（1328.99 ± 282.46）个/mm2]与 CUS＋KET 组（1224.76 ± 116.53）大鼠前额叶BDNF免疫反应阳性细胞数量上调,且CUS＋MT组前额叶BDNF阳性细胞数量较CUS＋KET组增加更显著,差异有统计学意义（t=2.537,P〈0.05）.（3）给药14 d 后,与 CUS 组[（495.14±109.01）个/mm2]相比,CUS＋KET组[（807.82±193.25）个/mm2]大鼠前额叶GluR1免疫反应阳性细胞数量升高,差异有统计学意义（t=2.386,P〈0.05）,而CUS＋MT组与CUS组比较,GluR1免疫反应阳性细胞数差异无统计学意义.结论 褪黑素具有与氯胺酮相似的抗抑郁作用.褪黑素抗抑郁的作用机理可能与前额叶BDNF表达上调有关.Objective To evaluate the antidepressant action of melatonin in stress model of depres-sion and the effects of the melatonin on depressive-like behavior.Methods Forty male Wistar rats were ran-domly divided into four groups（n=10）：controls group（CON）,chronic unpredictable mild stress group （CUS）,chronic unpredictable mild stress group ＋ melatonin group（CUS＋MT）and chronic unpredictable mild stress group ＋ketamine group（CUS＋KET）.The rats in CUS group,CUS＋MT group and CUS＋KET group were given different stress stimulation for 42 days to establish the chronic mild unpredictable stress ani-mal model.Sucrose preference experiments was used to detect the depression model and the level of depres-sion was tested by forced swim test.The influence of Short-term low doses of melatonin on the level of BDNF and GluR1 in the prefrontal cortex,was detected by immunohistochemistry（IHC）on 58 day after the start of the experiment.Results （1）The CUS showed depressant-like behavior,and the percent sucrose uptake scores and the cumulative immobility time of the CUS group were decreased significantly（P〈0.05）.（2）After injection melatonin 14 d,the cumulative immobility time of CUS＋MT group（（60.70±18.56）s）and CUS＋KET group（（56.43±20.46）s）were decreased significantly in comparison to the CUS group（146.34±34.10） s）.It was observed a highly significant（P〈0.05）decrease of and up-regulation of the BDNF cells in CUS＋MT group（（1 328.99±282.46）/mm2）and CUS＋KET group（（1 224.76±116.53）/mm2）in comparison to the CUS group,the number of BDNF cells in CUS＋MT group was increased significantly in comparison to the CUS＋KET group;（3）After administration drug 14 days,the number of GluR1 cells of CUS＋KET（（807.82± 153.25）/mm2）but not CUS＋MT（（632 ± 156.34）mm2）significantly increased compared with CUS （（807.82±193.25）/mm2）.Conclusion The results indicate that the melatonin induce an antidepressant-like action like ket

关 键 词：褪黑素 氯胺酮 抑郁症 慢性不可预期性应激 大鼠 

分 类 号：R-332[医药卫生] R749.4