海马改善斑马鱼慢性应激所致抑郁样行为和病理变化的机制  

Mechanism of seahorse ameliorating depression-like behavioral and pathological changes caused by chronic stress in zebrafish

作　　者：邓淑怡 王佳佳 张永平 钟绮媚[1,3] 杨志友 宋采 DENG Shu-yi;WANG Jia-jia;ZHANG Yong-ping;ZHONG Qi-mei;YANG Zhi-you;SONG Cai(Research Institute for Marine Drugs and Nutrition,College of Food Science and Technology,Guangdong Ocean University,Zhanjiang,Guangdong 524088,China;Shenzhen Research Institute,Guangdong Ocean University,Shenzhen,Guangdong 518120,China;Key Laboratory of Aquatic Product Processing and Safety,Guangdong Ocean University,Zhanjiang,Guangdong 524088,China)

机构地区：[1]广东海洋大学食品科技学院海洋药物研究所,广东湛江524088 [2]广东海洋大学深圳研究院,广东深圳518120 [3]广东海洋大学水产品加工与安全重点实验室,广东湛江524088

出　　处：《中国药理学通报》2023年第3期520-525,共6页Chinese Pharmacological Bulletin

基　　金：广东省省级科技计划项目(No 2016B020235001);广东省自然科学基金资助项目(No 2021A1515011579);深圳市科技计划(国际合作研究)项目(No GJHZ20190823111414825);湛江市科技项目(No 2021A05046)。

摘　　要：目的探究海洋中药海马对慢性不可预测温和应激(chronic unpredictable mild stress,CUMS)诱导的斑马鱼抑郁样模型的影响。方法将成年斑马鱼分为对照组、Stress组、Stress+低剂量(Stress+0.044%SH)、Stress+高剂量(Stress+0.22%SH)海马干预组,采用新环境水槽(novel tank test,NTT)鉴定抑郁样行为,Elisa检测皮质酮(cortisol)、白介素(interleukin,IL)-6和干扰素(interferon,IFN)-γ水平,高效液相色谱检测多巴胺(dopamine,DA)、去甲肾上腺素(norepinephrine,NE)、5-羟色胺(5-hydroxytryptamine,5-HT)及代谢产物含量,荧光定量PCR检测色氨酸羟化酶(tryptophan hydroxylase,TPH)-2、5-HT2A受体的mRNA表达水平。结果与对照组相比,Stress组在NTT中达到顶部的潜伏期明显延长,转移至顶部区域次数和顶部停留时间明显减少,cortisol和IL-6、IFN-γ蛋白水平明显上升,脑内DA和5-HT含量明显减少以及5-HT代谢率增加,同时5-HT2A mRNA表达上调,TPH2的mRNA表达下调;而低剂量的海马干预有效降低CUMS斑马鱼焦虑程度、减少cortisol和IL-6、IFN-γ浓度、增加单胺类神经递质水平和逆转5-HT能系统失调。结论海马可能通过抗炎和调节单胺类神经递质水平发挥抗抑郁效果。Aim To investigate the effect of marine herbal seahorse on chronic unpredictable mild stress(CUMS)-induced depression-like model in zebrafish.Methods Adult zebrafish were divided into control,Stress,Stress+low dose(Stress+0.044%SH)and Stress+high dose(Stress+0.22%SH)seahorse intervention groups,and depression-like behavior was iden-tified by novel tank test(NTT),cortisol,interleukin(IL)-6 and interferon(IFN)-γlevels were detected by ELISA.The levels of dopamine(DA),norepinephrine(NE),5-hydroxytryptamine(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)were determined by high performance liquid chromatography.The mRNA expression levels of tryptophan hydroxylase(TPH)-2 and 5-HT2A receptor were measured by real-time quantitative PCR.Results Compared with the control group,the Stress group showed significantly longer latency to reach the top in NTT,significantly reduced number of transfers to the top region and top residence time,significantly increased levels of cortisol and IL-6,IFN-γprotein,significantly reduced levels of DA and 5-HT in brain as well as increased metabolism rate of 5-HT,while 5-HT2A mRNA expression was up-regulated and TPH2 mRNA expression was down-regulated.In contrast,low-dose seahorse intervention effectively reduced anxiety,decreased cortisol and IL-6 and IFN-γconcentrations,increased monoamine neurotransmitter levels and reversed dysregulation of the 5-HT ergic system in CUMS zebrafish.Conclusion Seahorse may exert antidepressant effects through anti-inflammation and modulation of monoamine neurotransmitter levels.

关 键 词：海马 抑郁症 慢性不可预测温和应激 斑马鱼 神经递质 炎症 

分 类 号：R332[医药卫生—人体生理学] R282.74[医药卫生—基础医学] R364.5R749.42R749.72