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1-甲基海因对抑郁大鼠行为学的影响及机制初探
Effects of 1-methylhydantoin on behavior changes in depressive rats and its possible mechanisms

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游杰舒 1   张瑞睿 2   王春国 1   石晋丽 1   郭建友 2   史淑宁 1   候文慧 1   刘勇 1 *  
文摘 目的研究1-甲基海因的抗抑郁作用,并分析其可能的作用机制。方法采用慢性冰水游泳应激(chronic forcedswim stress)方法建立大鼠抑郁模型。氟西汀(10 mg·kg~(-1))和1-甲基海因(20,40和80 mg·kg~(-1))在造模完成后灌胃给药,每天1次,连续14 d。观察大鼠体重变化,并用旷场实验和蔗糖偏好实验检测大鼠行为学变化;用酶联免疫吸附法(ELISA)测定大鼠血清皮质酮的含量;用蛋白免疫印迹法(Western blot)分析大鼠海马中脑源性神经营养因子(BD-NF)蛋白的表达水平。结果与正常组比较,慢性应激大鼠的体重减少(P<0.01),在旷场实验中的运动距离减少(P<0.01),血清中皮质酮含量升高(P<0.01),海马中BDNF的蛋白表达降低(P<0.01)。与模型组比较,1-甲基海因40mg·kg~(-1)能改善抑郁大鼠体重的下降(P<0.05),增加旷场实验中的运动距离(P<0.01),降低大鼠血清皮质酮的水平(P<0.05),增加大鼠海马中BDNF的蛋白表达(P<0.01)。结论1-甲基海因具有明显的抗抑郁作用,其机制可能与调节下丘脑-垂体-肾上腺(HPA)轴功能和提高BDNF的表达有关。
其他语种文摘 Aim To study the antidepressive effects of 1-methylhydantoin on rats and to investigate the related mechanisms. Methods The rat model of depression was established by chronic forced swim stress. Fluoxetine (10 mg · kg ~(- 1) · d ~(- 1)) and 1-methylhydantoin (20,40 and 80 mg·kg ~(- 1)·d ~(- 1)) were administered after stress procedure for 14 days. Body weights were measured and depression-like behaviors were evaluated in the open-field test and sucrose preference test. Then the corticosterone levels in the rat plasma were determined by enzyme-linked immunosorbent assay (ELISA) and BDNF protein levels in the hippocampus were measured by western blotting analysis. Results Compared with control group,chronic forced swim stress caused significant decreases of body weight,total distances and BDNF levels,and a significant increase of the corticosterone level in the rat plasma. Compared with the model group,1-methylhydantoin (40 mg· kg ~(- 1)) could significantly improve body weight,total distances and BDNF levels in rats and reduce the corticosterone level in the rat plasma. Conclusion The results suggest that the antidepressive effects of 1-methylhydantoin is likely to be mediated by modulating the function of HPA axis and increasing the expression of BDNF in brain tissues.
来源 中国药理学通报 ,2013,29(8):1104-1108 【核心库】
DOI 10.3969/j.issn.1001-1978.2013.08.015
关键词 1-甲基海因 ; 抑郁 ; 慢性冰水游泳应激 ; 旷场实验 ; 蔗糖偏好实验 ; 下丘脑-垂体-肾上腺轴 ; 皮质酮 ; 脑源性神经营养因子
地址

1. 北京中医药大学中药学院, 北京, 100029  

2. 中国科学院心理研究所, 中国科学院心理健康重点实验室, 北京, 100101

语种 中文
文献类型 研究性论文
ISSN 1001-1978
学科 医药、卫生;基础医学;神经病学与精神病学;药学
基金 国家重大科技专项 ;  北京中医药大学研究生自主课题
文献收藏号 CSCD:4913676

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