慢性皮质酮注射诱导焦虑性抑郁树鼩模型的研究  

Study on model of tree shrew induced by chronic corticosterone injection in anxious depression

作　　者：吴梦瑶 赵洪庆[1] 杨琴[1] 柳卓[1] 杜青[1] 孟盼[1] 韩远山[1] 王宇红[1] 

机构地区：[1]湖南中医药大学,湖南省中药粉体与创新药物省部共建国家重点实验室培育基地,湖南长沙410208

出　　处：《中国药理学通报》2018年第1期141-145,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81403387);湖南省科技厅重点项目(No 2015DK3003)

摘　　要：目的探讨慢性皮质酮注射对近灵长类动物树鼩焦虑和抑郁样行为的影响,并进行药物预见性评价,建立新型焦虑性抑郁动物模型。方法12只中缅树鼩随机分为正常组、模型组和文拉法辛组,每组4只。采用慢性皮质酮注射(ih,27 mg·kg^(-1),21 d)建立焦虑性抑郁树鼩模型,文拉法辛组于造模同时灌胃给药(6 mg·kg^(-1))。采用自主活动评分、糖水偏好测试、Morris水迷宫实验评价树鼩的焦虑和抑郁行为表现;ELISA试剂盒检测树鼩血浆CRH、ACTH、COR含量;HPLC-ECD法检测树鼩脑内海马、杏仁核、前额叶皮质的单胺递质5-HT、NE、DA含量。结果与正常组比较,模型组树鼩自主活动评分、糖水偏食度、学习记忆能力均明显下降(P<0.01),血浆CRH、ACTH、COR含量明显上升(P<0.05),海马、杏仁核、前额叶皮质5-HT、NE、DA含量降低(P<0.05);文拉法辛组树鼩学习记忆能力得到改善,血浆CRH、COR含量明显降低(P<0.05),各脑区5-HT、NE、DA含量上升(P<0.05)。结论焦虑性抑郁模型树鼩具有明显的HPA轴亢进及单胺递质失调现象,而文拉法辛能够逆转该现象,说明该焦虑性抑郁树鼩模型具有药物预见性,是一种更接近人类临床的新型焦虑性抑郁动物模型。AimTo investigate the effects of chronic corticosterone injection on anxiety and depression-like behavior of tree shrews,evaluate the predictability of drug and establish a novel animal model of anxious depression.Methods Twelve Chinese and Burma tree shrews were randomly divided into normal group,model group and venlafaxine group.The anxious depression model of tree shrew was established by chronic corticosterone injection(ih,27 mg·kg^(-1),21 d).The venlafaxine group received intragastric administration(6 mg·kg^(-1)).Autonomous activity score,sugar water preference test and Morris water maze test were used to evaluate the anxiety and depression-like behavior of tree shrews.The expressions of CRH,ACTH and COR in the tree shrew plasma were determined by Elisa kit.The contents of monoamine neurotransmitters of tree shrews in the hippocampus,amygdala and prefrontal cortex were detected by HPLC-ECD.ResultsCompared with the normal group,the autonomous activity score,sugar water partial eclipse degree and the learning and memory ability significantly decreased(P<0.01),while the contents of CRH,ACTH and COR significantly increased(P<0.05),and the contents of 5-HT,NE and DA in the hippocampus,amygdala and prefrontal cortex declined in the model group(P<0.05).In the venlafaxine group,the learning and memory abilities of the tree shrews were improved,the levels of CRH and COR in plasma were significantly decreased(P<0.05),and the contents of 5-HT,NE and DA were increased(P<0.05).Conclusions The tree shrews of anxious depression have obvious HPA axis hyperactivity and monoamine neurotransmitter disorder,and venlafaxine can reverse this phenomenon,indicating that the tree shrews model of anxious depression has drug predictability,which is a kind of novel animal model of anxious depression closer to human in clinic.

关 键 词：焦虑 抑郁 树鼩 文拉法辛 HPA轴 单胺递质 皮质酮 

分 类 号：R-332[医药卫生] R322.81