二仙汤对迟发性抑郁症模型大鼠脑组织脉络丛叶酸转运-海马神经发生的影响  

Effects of Erxian Decoction(二仙汤)on Choroid Plexus Folate Transport-Hippocampal Neurogenesis in Rat Brain Tissue of Late-Onset Depression Model

作　　者：李兰心 曾宁溪 张天鸽 严灿[1] 吴丽丽[1] LI Lanxin;ZENG Ningxi;ZHANG Tiange;YAN Can;WU Lili(Basic Research Center for Integrated Traditional Chinese and Western Medicine,Guangzhou University of Chinese Medicine,Guangzhou,510006;Longhua District People's Hospital)

机构地区：[1]广州中医药大学中西医结合基础研究中心,广东广州510006 [2]深圳市龙华区人民医院

出　　处：《中医杂志》2024年第10期1046-1055,共10页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81774102,82174255)。

摘　　要：目的探讨二仙汤治疗迟发性抑郁症(LOD)的效果及可能作用机制。方法40只雄性7~8周龄Wistar大鼠分为正常组和青年抑郁组各20只。60只20月龄雄性Wistar大鼠分为衰老组、迟发抑郁组、二仙汤组各20只。青年抑郁组大鼠采用慢性不可预计应激刺激(CUMS)6周建立抑郁模型,迟发抑郁组、二仙汤组衰老大鼠采用CUMS 6周建立LOD模型,正常组和衰老组不进行任何干预。造模的同时进行灌胃给药,二仙汤组大鼠给予二仙汤8 g/(kg·d)灌胃,正常组、青年抑郁组、衰老组、迟发抑郁组给予4 ml/(kg·d)纯净水灌胃,各组均给药6周。采用糖水偏爱实验、强迫游泳实验评估大鼠抑郁样行为,旷场实验评价大鼠自发活动能力,T迷宫实验评估大鼠认知功能;Western Blot法检测海马组织神经元核心抗原(NeuN)、巢蛋白、双皮质素(DCX)及脉络丛组织中闭锁小带蛋白1(ZO-1)、叶酸α受体(FRα)、还原型叶酸转运体(RFC)、质子耦合叶酸转运体(PCFT)蛋白表达;采用免疫荧光法检测海马齿状回Ki-67/巢蛋白双阳性细胞数、5-溴脱氧尿嘧啶核苷(BrdU)/DCX双阳性细胞数及脉络丛组织中ZO-1、FRα、RFC、PCFT蛋白表达;ELISA法检测血浆、脑脊液、海马组织中5-甲基四氢叶酸(5-MTHF)含量;采用Pearson相关分析对各组大鼠脑脊液、海马组织中5-MTHF含量与海马组织中巢蛋白、DCX、NeuN蛋白表达进行相关性分析。结果与正常组比较,青年抑郁组及迟发抑郁组大鼠糖水偏爱度降低,旷场总路程、穿格次数减少,强迫游泳不动时间延长,海马组织NeuN、巢蛋白、DCX蛋白表达均降低,海马齿状回Ki-67/巢蛋白双阳性细胞数、BrdU/DCX双阳性细胞数减少,ZO-1、FRα蛋白表达及荧光强度减少(P<0.05或P<0.01);青年抑郁组大鼠第3、4天及迟发抑郁组大鼠第2~4天T迷宫正确率均明显降低,迟发抑郁组大鼠脑脊液、海马组织中5-MTHF含量明显降低(P<0.05或P<0.01)。与青年抑郁组�Objective This study aims to investigate the effectiveness and potential mechanism of Erxian Decoction(二仙汤)for late-onset depression(LOD).Methods Forty Wistar male rats of 7-8 weeks were divided into 20each of normal group and youth depression group.Sixty Wistar male rats of 20 months were divided into 20 each of elder group,LOD group and Erxian Decoction group.The rats in youth depression group were modelled with chronic unpredictable mild stress(CUMS)for 6 weeks to build a depression model,and the elder rats in LOD group and Erxian Decoction group were modelled with CUMS for 6 weeks to build a LOD model,with no interventions in the normal group and the elder group.Gastric administration was carried out at the same time of modelling,rats in Erxian Decoction group were given 8 g/(kg·d)of Erxian Decoction by gavage,and rats in the normal group,youth depression group,elder group,and LOD group were given 4 ml/(kg·d)of pure water by gavage,for 6 weeks in each group.Sugar water preference experiment and forced swimming experiment were used to evaluate the depression-like behaviour of rats,absent field experiment was used to evaluate the spontaneous activity ability of rats,and T-maze experiment was used to evaluate the cognitive function of rats;Western blot assay was used to detect neuronal nuclei(NeuN),nestin,doublecortin(DCX)in hippocampal tissue,and zonula occludens-l(ZO-1),folate receptorα(FRα),reduced folate carrier(RFC),and protoncoupledfolate transporter(PCFT)protein expression in choroid plexus;immunofluorescence was used to detect the number of double-positive cells for Ki-67/nestin,the number of double-positive cells for 5-bromodeoxyuracil nucleoside(BrdU)/DCX in hippocampal dentate gyrus,and the protein expression of ZO-1,FRα,RFC,and PCFT in choroid plexus tissues;ELISA technique was used to detect plasma,cerebrospinal fluid,5-methyltetrahydrofolate(5-MTHF)in hippocampal tissues;Pearson correlation analysis was used to correlate the 5-MTHF content in cerebrospinal fluid and hippocampal tissues a

关 键 词：迟发性抑郁症 二仙汤 脉络丛 叶酸 神经发生 认知功能 

分 类 号：R285.5[医药卫生—中药学]