帕罗西汀片对抑郁症大鼠模型抑郁行为的改善效果及相关作用机制分析

目的 分析帕罗西汀片对改善抑郁症大鼠模型抑郁行为的效果,同时对相关作用机制进行探讨。方法 选取健康雄性SD大鼠63只,并随机分为参照组(n=21)、试验组(n=21)及模型组(n=21)。正常饲养参照组大鼠,试验组大鼠及模型组大鼠在孤养及慢性轻度不可预见刺激条件下进行抑郁症大鼠模型构建,模型建立期间对试验组大鼠实施帕罗西汀灌胃操作,对模型组及参照组大鼠实施0.9%NaCl灌胃操作,分析帕罗西汀片对抑郁症大鼠自主活动次数、不动时间、记忆能力及学习能力大鼠海马CA3区TrkB、BDNF蛋白表达产生的影响。结果 试验组大鼠自主活动次数明显较模型组多,试验组及模型组大鼠自主活动次数均明显少于参照组大鼠,差异有统计学意义(P0.05)。Morris水迷宫定位航行实验结果显示,试验组大鼠潜伏期第1～4天均明显短于模型组,试验组、模型组Morris水迷宫空间探索实验穿台次数明显多于参照组,差异有统计学意义(P0.05)。免疫组化染色结果表明大鼠海马CA3区BDNF蛋白阳性着色为棕褐色,TrkB着色亦为棕褐色,与参照组及试验组相比,模型组阳性着色明显减少且染色强度明显下降。模型组大鼠TrkB及BDNF蛋白阳性细胞占比均显著低于参照组及试验组(P0.05);试验组大鼠TrkB及BDNF蛋白阳性细胞占比较参照组低,差异有统计学意义(P0.05)。结论 帕罗西汀片能够使抑郁症大鼠抑郁症状得到明显改善,同时还能使大鼠记忆能力以及学习能力得到提高,作用机制与海马CA3区TrkB及BDNF蛋白表达获得上调存在一定的相关性。

Ameliorative efficacy of paroxetine tablets against depressive behavior in depression rat models and the mechanism behind it

Objective To analyze the ameliorative effects of paroxetine tablets on depressive behavior in depression rat models and explore the relevant mechanism.Methods Sixty-three healthy male Sprague-Dawley(SD) rats were randomly divided into the control group(n=21),the test group(n=21) and the model group(n=21).Rats in the control group were normally housed,and those in the test and model groups were housed individually under chronic unpredictable mild stress (CUMS) to establish depression rat models.Rats in the test group were intragastrically administered with paroxetine during the establishment of the depression model,and those in the control and model groups were merely intragastrically administered with 0.9% NaCl.Effects of paroxetine on locomotor activity,freezing time,memory and learning ability,and the protein expressions of brain-derived neurotrophic factor(BDNF) and its receptor TrkB in the CA3 hippocampus in depression rats were analyzed.Results The locomotor activity significantly increased in the test group compared with the model group,and it significantly decreased in the test and model groups compared with the control group,with statistically significant differences(P<0.05).In the Morris water maze(MMM)trials,the test group showed a shorter latency than the model group from Day 1 to Day 4.The test and model groups presented more platform-crossing numbers than the control group,with statistically significant differences(P<0.05).Immumohistochemical staining showed that BDNF-positive neurons(brown)and TrkB-positive neurons(brown)in the CA3 region significantly decreased with lower staining intensity in the model group compared with the control and test groups.Proportions of both TrkB-and BDNF-positive neurons in the model group were lower that those in the control and test groups(P<0.05).Proportions of TrkB-and BDNF-positive neurons in the test group were lower than those in the control group,with statistically significant differences(P<0.05).Conclusion Paroxetine tablets significantly improved depressive behavior in depression rats with enhanced memory and learning ability.This effect perhaps associated with the up-regulations of TrkB and BDNF in the CA3 hippocampus.