橙皮油素改善慢性应激小鼠焦虑抑郁样行为的作用及机制研究  

Effects and mechanism of auraptene on anxiety and depression-like behaviors in mice induced by chronically unpredicted mild stress

作　　者：张冬靓 李龙飞 张露文 欧阳一楠 毕文鹏[1] 孙连平[1] 于海玲[1] ZHANG Dongliang;LI Longfei;ZHANG Luwen;OUYANG Yinan;BI Wenpeng;SUN Lianping;YU Hailing(College of Medicine,Yanbian University,Yanji 133002,China)

机构地区：[1]延边大学医学院,吉林延吉133002

出　　处：《沈阳药科大学学报》2025年第3期262-273,共12页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81960656);吉林省科技厅自然科学基金项目(YDZJ202401048ZYTS)。

摘　　要：目的观察橙皮油素(auraptene,AUR)对慢性应激抑郁模型小鼠行为学改变的影响并探讨其作用机制。方法构建小鼠慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)抑郁模型。60只小鼠随机分为正常对照组(normal control group)、CUMS模型组、氟西汀组、AUR(2.5、5、10 mg·kg^(-1))组。实验最后2天内测试其抑郁相关行为学变化;实验第29天小鼠麻醉后取脑;酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)方法检测小鼠海马组织中色氨酸(tryptophan,TRP)、5-羟色胺(5-hydroxytryptamine,5-HT)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、核因子κB P65(nuclear factor kappa B P65,NF-κB P65)、白介素-6(interleukin-6,IL-6)和白介素-10(interleukin-10,IL-10)的含量;免疫组化法观察小鼠海马CA1和CA3区突触素(synaptophysin,SYP)和生长相关蛋白43(growth associated protein-43,GAP43)的表达;苏木精-伊红(hematoxylin-eosin,HE)染色法观察小鼠海马CA1和CA3区锥体细胞的形态和数量。结果与CUMS模型组相比,AUR各剂量组增加小鼠的体质量获得、减少强迫游泳实验(forced swimming test,FST)中的累计不动时间、增加旷场实验(open field test,OFT)中的运动时间和运动距离、增加高架十字迷宫(elevated plus maze,EPM)中的开臂滞留时间并减少其闭臂滞留时间、增加高架零迷宫(elevated zero maze,EZM)中的总运动时间和开臂滞留时间;上调小鼠海马组织中的TRP和5-HT含量;降低海马中TNF-α和NF-κB P65、IL-6含量,增加海马中IL-10含量;上调小鼠海马CA1和CA3区中SYP和GAP43的阳性表达(P<0.05或P<0.01);增加小鼠海马CA1和CA3区的锥体细胞数量。结论AUR减轻CUMS小鼠的焦虑抑郁样行为,其机制可能与缓解慢性应激诱导的小鼠海马组织TRP、5-HT的缺乏以及改善海马脑区的神经炎性和突触可塑性相关。Objective To observe the effects of Auraptene(AUR)on behavioral changes in depression model mice induced by chronic stress and explore its mechanism.Methods A mouse model of chronic unpredictable mild stress(CUMS)was established.The mice(n=60)were randomly divided into normal control(NC)group,CUMS model group,CUMS+fluoxetine(10 mg·kg^(-1))group,CUMS+AUR(2.5,5,10 mg·kg^(-1))groups.On the 8th day the CUMS procedure,fluoxetine,different doses of AUR were continuously administered for 21 days.The body weight and the related behavioral changes within the last two days of the experiment were monitored.On the 29th day of the experiment,mice were anesthetized and their brains were removed.Tryptophan(TRP),5-hydroxytryptamine(5-HT),tumor necrosis factor(TNF-α),nuclear factorκB P65(NF-κB P65),interleukin-6(IL-6),and interleukin-10(IL-10)in mouse hippocampus were detected by enzyme linked immunosorbent assay(ELISA).Immunohistochemistry was used to observe the expression of synaptophysin(SYP)and growth associated protein 43(GAP43)in CA1 and CA3 regions of mouse hippocampus.HE staining was used to observe the morphology of pyramidal cell in CA1 and CA3 regions of mouse hippocampus.Results Compared with the CUMS model group,AUR increased the weight gain of mice,locomotion time and distance in open field experiments(OFT);increased the open arm retention time and reduced closed arm retention time in elevated cross maze(EPM);increased the total locomotion time and open arm retention time in elevated zero maze(EZM);and shorten the immobility time in forced swimming test(FST);up-regulated the protein expressions of SYN and GAP43 in hippocampus of CUMS model mice;and increased the number of neurons and improved the morphological abnormalities of nerve cells in hippocampus.Conclusion AUR alleviates anxiety and depression like behaviors in CUMS mice,and its mechanism may be related to alleviating the deficiency of TRP and 5-HT,as well as improving neuroinflammation and synaptic plasticity in the hippocampus of mice induced by chro

关 键 词：橙皮油素 慢性不可预见性温和应激 单胺类递质 神经炎症 突触可塑性 小鼠 

分 类 号：R964[医药卫生—药理学]