丙戊酸钠抗抑郁作用涉及改善氧化应激平衡和提升脑源性神经营养因子表达

中国临床药理学与治疗学 ›› 2015, Vol. 20 ›› Issue (5): 481-485.

• 基础研究 • 下一篇

丙戊酸钠抗抑郁作用涉及改善氧化应激平衡和提升脑源性神经营养因子表达

刘任, 邱红梅, 蒋兴惠, 姚欣凯, 吴亚陵, 周岐新

重庆市生物化学与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:2014-09-04 修回日期:2014-10-27 发布日期:2015-06-11
通讯作者: 周岐新,男,博士生导师,研究方向:神经精神药理学。Tel: 13527534910 E-mail: cqzhouqx60@aliyun.com
作者简介:刘任,男,硕士研究生,研究方向:神经精神药理学。Tel: 15215020838 E-mail: 2445830811@qq.com
基金资助:
重庆市科委基金课题(cstc2013jcjA10040);重庆市教委基金课题(KJ1400208)

Anti-depressive effects of valproate involved in improvement of oxidative stress balance and elevation of BDNF expression in CUS-induced rat depression model

LIU Ren, QIU Hong-mei, JIANG Xing-hui, YAO Xin-kai, WU Ya-ling, ZHOU Qi-xin

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

Received:2014-09-04 Revised:2014-10-27 Published:2015-06-11

摘要/Abstract

摘要： 目的: 探讨丙戊酸钠减轻慢性不可预见刺激(CUS)致大鼠抑郁行为是否与改善机体氧化应激功能及脑源性神经营养因子(BDNF)表达有关。方法: 雄性SD大鼠60只,随机分为对照组(CG),模型组(MG),丙戊酸钠灌胃正常组(VAPC)和丙戊酸钠灌胃模型组(VAPM)。以开场试验和强迫游泳试验评价大鼠焦虑抑郁行为;采用常规生物化学方法测定大脑皮质丙二醛(MDA)含量及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活力;荧光定量PCR和Western blot检测海马脑源性神经营养因子(BDNF)mRNA和蛋白表达。结果: 与CG组相比,MG组大鼠开场试验水平得分和垂直得分明显降低,强迫游泳试验不动时间显著延长,MDA含量升高,SOD及CAT活力明显下降,海马BDNF mRNA和蛋白表达均明显降低。给予丙戊酸钠可明显阻遏上述变化,但对正常大鼠无明显影响。结论: CUS致大鼠焦虑抑郁行为与体内氧化及抗氧化失衡,海马BDNF表达减少有关;丙戊酸钠能阻遏这种变化,从而显示减轻CUS所致大鼠焦虑抑郁行为作用。

关键词: 抑郁症, 慢性不可预见刺激, 丙戊酸钠, 氧化应激, 脑源性神经营养因子

Abstract: AIM: To investigate if the improvement of oxidative stress function and BDNF expression is associated with anti-depressive effect of valproate in chronic unpredictable stress (CUS)-induced rat depression model.METHODS: Sixty male SD rats were randomly divided into control group (CG), model group (MG), valproate-treated control group (VAPC), and valproate-treated model group (VAPM). The open field test (OFT) and forced swim test (FST) were used to evaluate depressive behaviors. Biochemistry kits were used to determine activity of SOD and CAT as well as MDA level from the cerebral cortex, and real time PCR and Western blot were used to determine expression of BDNF mRNA and protein of hippocampus.RESULTS: Compared with CG, the open field score, SOD activity as well as CAT activity were decreased significantly, the immobility time of FST and level of MDA were increased significantly in MG rats; meanwhile both mRNA and protein expression of BDNF in hippocampus were decreased obviously in MG rats. The treatment of valproate obviously blunted the changes above caused by CUS, but failed to affect that from CG rats.CONCLUSION: Improvement of oxidative stress response and elevation of BDNF expression may be responsible for anti-depressive effect of valproate in CUS-induced rat depression model.

Key words: depression, chronic unpredictable stress, valproate, oxidative stress, BDNF

中图分类号:

刘任, 邱红梅, 蒋兴惠, 姚欣凯, 吴亚陵, 周岐新. 丙戊酸钠抗抑郁作用涉及改善氧化应激平衡和提升脑源性神经营养因子表达[J]. 中国临床药理学与治疗学, 2015, 20(5): 481-485.

LIU Ren, QIU Hong-mei, JIANG Xing-hui, YAO Xin-kai, WU Ya-ling, ZHOU Qi-xin. Anti-depressive effects of valproate involved in improvement of oxidative stress balance and elevation of BDNF expression in CUS-induced rat depression model[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(5): 481-485.

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丙戊酸钠抗抑郁作用涉及改善氧化应激平衡和提升脑源性神经营养因子表达

Anti-depressive effects of valproate involved in improvement of oxidative stress balance and elevation of BDNF expression in CUS-induced rat depression model

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