文拉法辛抗CUMS致大鼠抑郁行为涉及阻遏海马TH和TPH表达下调

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (4): 398-403.

文拉法辛抗CUMS致大鼠抑郁行为涉及阻遏海马TH和TPH表达下调

秦丽娟, 刘丹, 蒋兴惠, 邱红梅, 汪丽佳, 刘任, 费慧芝, 胡小娅, 周岐新

重庆市生物化学及分子药理学重点实验室,重庆医科大学药理学教研室,重庆400016

收稿日期:2013-11-06 修回日期:2014-03-21 出版日期:2014-04-26 发布日期:2020-07-24
通讯作者: 周岐新,通信作者,男,博士生导师,研究方向:神经精神药理学。Tel:023-68485038 E-mail:cqzhouqx60@aliyun.com
作者简介:秦丽娟,女,硕士研究生,研究方向:神经精神药理学。Tel:13896443619 E-mail:qlj327@126.com

Down-regulation of hyppocampal TH and TPH expression involved in CUMS-induced depressive behaviors of rats and interfering effects of venlafaxine

QIN Li-juan, LIU Dan, JIANG Xing-hui, QIU Hong-mei, WANG Li-jia, LIU Ren, FEI Hui-zhi, HU Xiao-ya, ZHOU Qi-xin

Key Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China

Received:2013-11-06 Revised:2014-03-21 Online:2014-04-26 Published:2020-07-24

摘要/Abstract

摘要： 目的: 探讨慢性轻度不可预见刺激(chronic unpredictable mild stress,CUMS)致大鼠抑郁行为与海马色氨酸羟化酶(tryptophan hydroxylase,TPH)和酪氨酸羟化酶(tyrosine hydroxylase,TH)表达关系及文拉法辛的干预作用。方法: 雄性SD大鼠64只,随机分为对照组(NG)、模型组(MG)、文拉法辛灌胃正常组(WNG)、文拉法辛灌胃模型组(WMG)。采用孤养结合CUMS方式建立大鼠抑郁症模型;以开场实验和强迫游泳实验评价大鼠焦虑抑郁行为;生物化学方法检测大鼠皮层超氧化物歧化酶(superoxide dismutase,SOD)活力以及丙二醛(malondialdehyde, MDA)含量;荧光定量PCR和Western-blot分别测定海马TPH、TH mRNA和蛋白表达。结果: 与NG组相比,MG组大鼠开场实验水平得分、垂直得分明显降低,强迫游泳不动时间显著延长,MDA含量升高, SOD活力及TPH、TH mRNA和蛋白表达均明显下降;给予文拉法辛可明显阻遏CUMS诱导的上述变化,但对正常大鼠无影响。结论: CUMS致大鼠抑郁行为与海马TH和TPH表达下调有关;文拉法辛能阻遏这种表达下调,改善大鼠焦虑和抑郁症状。

关键词: 抑郁症, 慢性轻度不可预见刺激, 文拉法辛, 海马色氨酸羟化酶, 酪氨酸羟化酶

Abstract: AIM: To investigate if chronic unpredictable mild stress (CUMS)-induced anxiety-depression-like behaviors of rats is associated with the expression changes of hyppocampal TH and TPH and interfering effects of venlafaxine. METHODS: Sixty-four male SD rats were randomly divided into normal group (NG), model group (MG), Venlafaxine -treated normal group (WNG), and Venlafaxine -treated model group (WMG).CUMS with solitary condition was taken to establish rat depression model.The open field test (OFT) and Forced swim test (FST) were used to evaluate depressive behaviors, biochemistry kit, real-time PCR, and western blot were used to determine SOD activity and MDA level of cortex, as well as mRNA and protein expressions of hippocampus TPH and TH. RESULTS: Compared with corresponding control, the open field score (ambulation and rearing), cortex SOD activity, as well as mRNA and protein expression of hippocampus TPH and TH significantly were decreased with obviously increasing cortex MDA and immobility time of FST in MG. The treatment of Venlafaxine obviously blunted the changes above caused by CUMS, but failed to affect normal rats. CONCLUSION: CUMS-induced depression of rats is associated with down-regulation of hyppocampal TH and TPH expression, which can be blunted by administration of Venlafaxine.

Key words: depression, CUMS, venlafaxine, TPH, TH

中图分类号:

秦丽娟, 刘丹, 蒋兴惠, 邱红梅, 汪丽佳, 刘任, 费慧芝, 胡小娅, 周岐新. 文拉法辛抗CUMS致大鼠抑郁行为涉及阻遏海马TH和TPH表达下调[J]. 中国临床药理学与治疗学, 2014, 19(4): 398-403.

QIN Li-juan, LIU Dan, JIANG Xing-hui, QIU Hong-mei, WANG Li-jia, LIU Ren, FEI Hui-zhi, HU Xiao-ya, ZHOU Qi-xin. Down-regulation of hyppocampal TH and TPH expression involved in CUMS-induced depressive behaviors of rats and interfering effects of venlafaxine[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(4): 398-403.

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