摘要
目的 研究增龄对小鼠焦虑抑郁样行为以及海马炎症因子和色氨酸(TRP)的影响。方法 选取24只C57BL/6J小鼠,分别是3月龄(青龄组)、12月龄(中龄组)和18月龄(老龄组),每组各8只。通过高架十字迷宫和强迫游泳实验评估小鼠的焦虑抑郁样行为;高效液相色谱法测定海马TRP含量;ELISA法检测海马中干扰素γ(IFN-γ)、白细胞介素6 (IL-6)、肿瘤坏死因子α(TNF-α)和IL-10的含量;并用Western-Blotting法检测海马吲哚胺2,3-双加氧酶-1 (IDO1)的表达水平。结果 高架十字迷宫实验结果显示:老龄组小鼠与青、中龄组小鼠比较,进入开放臂的时间明显减少(P <0. 05)。在强迫游泳实验中,老龄组小鼠与青、中龄组小鼠比较,不动时间显著增加(P <0. 05)。老龄组小鼠海马TNF-α含量和IDO1蛋白表达水平显著高于青、中龄组小鼠(P <0. 05),而海马TRP含量明显减少(P <0. 05)。结论 增龄会导致焦虑抑郁行为增加,伴随着海马炎症反应,以及TRP水平下降,推测增龄通过炎症反应影响TRP代谢通路,参与了老年抑郁症的发病机制。
Objective To investigate the effects of ageing on anxiety-and depressive-like behaviors,inflammatory cytokines and tryptophan(TRP)in hippocampus of mice.Methods C57BL/6J mice were divided into young mice group(3 months old),middle-aged mice group(12 months old)and old mice group(18 months old),with 8 mice in each group.Anxiety-and depressive-like behaviors in mice were evaluated by elevated plus maze and forced swimming test.Tryptophan content in hippocampus was determined by high performance liquid chromatography.The levels of interferon-γ(IFN-γ),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α)and interleukin-10(IL-10)in hippocampus were detected by ELISA.Indoleamine 2,3-dioxygenase-1(IDO1)expression in hippocampus was detected by western-blotting.Results In the elevated plus maze test,the time spent in the open arms in old mice group was significantly shorter than that in young and middle-aged mice group(P<0.05).In the forced swimming test,the immobility time in old mice group was significantly longer than that in young and middle-aged mice group(P<0.05).The expression levels of TNF-αand IDOl in hippocampus of old mice group were significantly higher than those of young and middle-aged mice group(P<0.05),while the content of tryptophan was significantly lower(P<0.05).Conclusion Ageing might increase the anxiety-and depressive-like behaviors,induce hippocampal inflammation and the decrease of tryptophan level.It is speculated that ageing affects tryptophan metabolism pathway through inflammation and participates in the pathogenesis of geriatric depression.
作者
李楠楠
王奇
林易玮
张夏
礼希曦
齐国先
Li Nannan;Wang Qi;Lin Yiwei;Zhang Xia;Li Xixi;Qi Guoxian(Department of Geriatrics Cardiology,First Hospital of China Medical University,Shenyang,110001,China;Department of Psychiatry,The First Hospital of China Medical University,Shenyang,110001,China)
出处
《国际老年医学杂志》
2020年第6期345-348,363,共5页
International Journal of Geriatrics