甘草总黄酮抗大鼠应激抑郁作用及对突触可塑性关键蛋白SYP/PSD-95的调节作用  

Antidepressant effect of licorice flavonoids from Glycyrrhiza uralensis on stress-induced depression and the key protein SYP/PSD95 associated with synaptic plasticity in rats

作　　者：华冰[1] 程瑞凤[1] 景晶[1] 薛旻秋 赵伟鸿[1] 樊紫周[1] 果嘉[1] 杨卫东[1] 王英华 彭晓东[1,3] 

机构地区：[1]宁夏医科大学药学院药理学系,银川750004 [2]宁夏药检所,银川750004 [3]宁夏颅脑疾病重点实验室,银川750004

出　　处：《中国新药杂志》2014年第10期1180-1187,共8页Chinese Journal of New Drugs

基　　金：国家自然科学基金(81060113)

摘　　要：目的:探讨甘草总黄酮(LF)的抗大鼠慢性不可预知应激抑郁作用机制。方法:将40只雄性SD大鼠,随机分为正常对照组、模型组、甘草总黄酮组(100,300 mg·kg-1)和氟西汀阳性药物组(10 mg·kg-1);采用9种不同刺激方式给予刺激建立慢性不可预知应激抑郁模型(CUS)的同时,分别灌胃给予相应剂量的药物及等体积溶剂实施干预,共28 d。建模及药物干预结束后,分别采用强迫游泳实验(FST)、悬尾实验(TST)和旷场实验(OFT)评价甘草总黄酮的抗应激抑郁行为作用,免疫组织化学法及Western Blot蛋白印迹法检测海马组织中突触结构蛋白突触素(SYP)和突触后致密物质-95(PSD-95)的蛋白表达变化,qRT-PCR法检测相关蛋白的mRNA的表达情况。结果:经过28 d慢性不可预知应激刺激,模型组大鼠表现出TST和FST不动时间明显延长,OFT中水平活动数、垂直活动数和修饰次数明显减少,粪便粒数明显增多等抑郁行为,应激大鼠伴有海马组织中SYP蛋白及mRNA表达的减少和PSD-95蛋白及mRNA表达的增多;甘草总黄酮100,300mg·kg-1能够明显缩短应激大鼠的TST和FST不动时间,增加OFT中应激大鼠水平活动数、垂直活动数和修饰次数,及减少粪便粒数;甘草总黄酮100,300 mg·kg-1能够明显增加海马组织中SYP蛋白及mRNA表达,降低PSD-95蛋白及mRNA的表达。结论:甘草总黄酮可能是通过对突触可塑性关键蛋白表达的调节发挥其抗慢性不可预知应激抑郁作用。Objective： To investigate the antidepressant effect and related mechanism of the licorice flavonoids（LF） from the Glycyrrhiza uralensis. Methods： Male Sprague-Dawley rats（n = 60） were randomly divided into 5 groups. The rats were exposed to 9 kinds of sequent stressors in an unpredictable order and at an unpre-dictable time of the day for 28 day. Fluoxetine（10 mg·kg- 1） or flavonoids（100 and 300 mg·kg- 1） were intragastrically administrated once a day accordingly. The forced swimming test（ FST）,tail suspension test（ TST） and open field test（OFT） were employed to elucidate the antidepressant effects. The protein expression levels of synaptophysin（SYP） and postsynaptic density-95（PSD-95） in the hippocampus were measured by immunocytochemistry and Western-blotting analysis,and the mRNA expression levels of SYP and PSD-95 were analyzed by qRTPCR,respectively. Results： The flavonoids showed an antidepressant effect in rat CUS model. The flavonoids significantly up-regulated the protein and mRNA expression levels of SYP and down-regulated the protein and mRNA expression levels of PSD-95 in the hippocampus. Conclusion： The antidepressant effect of the licorice flavonoids from Glycyrrhiza uralensis may relate to modulate the expression of the critical proteins associated with synaptic structural and plasticity in the hippocampus.

关 键 词：甘草 黄酮 抑郁症 应激 突触素 突触后致密物-95 

分 类 号：R965.1[医药卫生—药理学] R975.5[医药卫生—药学]