艾司西酞普兰联合有氧运动对小鼠抑郁症的治疗作用  

Effects of Escitalopram combined with aerobic exercise on depression in mice

作　　者：孙一鸣 谷昱琛 黄莹莹[1,2] 梁心 鲁明 刘哲 SUN Yiming;GU Yuchen;HUANG Yingying;LIANG Xin;LU Ming;LIU Zhe(Department of Pharmacy,First Affiliat-ed Hospital of Bengbu Medical College,Bengbu 233000,China;Department of Pharmacology,School of Pharmacy,Bengbu Medical College;Department of Pharmacology,School of Basic Medicine,Nanjing Medical University)

机构地区：[1]蚌埠医学院第一附属医院药剂科,蚌埠233000 [2]蚌埠医学院药学院药理教研室 [3]南京医科大学基础医学院药理教研室

出　　处：《山西医科大学学报》2021年第12期1576-1583,共8页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(81573403);安徽省高校自然科学研究重点项目(KJ2020A0589);蚌埠医学院第一附属医院优秀青年科学基金项目(2019byfyyq06);蚌埠医学院自然科学重点项目(BYKY2019024ZD)。

摘　　要：目的探究艾司西酞普兰联合有氧运动对抑郁模型小鼠的抗抑郁作用及其机制。方法以C57BL/6小鼠为研究对象,采用慢性温和不可预知应激模型进行抑郁小鼠模型的制备,实验分为空白对照组(n=7)、模型组(n=7)、艾司西酞普兰组(n=7)、联合治疗组(艾司西酞普兰+有氧运动,n=7)。通过糖水偏好实验、强迫游泳实验、悬尾实验、旷场实验评价小鼠抑郁样行为。利用高效液相仪检测各组小鼠海马脑区氨基酸水平。ELISA法检测各组小鼠外周血炎症因子水平。免疫荧光或蛋白质免疫印迹法检测小鼠海马脑区GFAP及焦亡相关蛋白GSDMD、Caspase-1表达水平。结果与对照组相比,模型组小鼠糖水偏好率、旷场实验运动总路线长度及海马脑区GFAP表达减少,强迫游泳实验及悬尾实验不动时间、外周血促炎因子含量,海马脑区牛磺酸、γ-氨基丁酸水平及GSDMD、Caspase-1成熟体表达增加,差异均有统计学意义(P<0.05)。与模型组相比,艾司西酞普兰组及联合治疗组小鼠糖水偏好率、旷场实验运动总路线及海马脑区GFAP表达增加,强迫游泳实验及悬尾实验不动时间、外周血促炎因子、海马脑区牛磺酸、γ-氨基丁酸含量及GSDMD、Caspase-1成熟体表达减少,差异均有统计学意义(P<0.05)。与艾司西酞普兰组相比,联合治疗组旷场实验总路线显著增加(P<0.05),小鼠糖水偏好率、海马脑区GFAP表达有增加趋势,强迫游泳实验及悬尾实验不动时间、外周血促炎因子、海马脑区牛磺酸、γ-氨基丁酸含量及GSDMD、Caspase-1成熟体表达显示减少趋势,但差异均无统计学意义(P>0.05)。结论艾司西酞普兰联合有氧运动对抑郁模型小鼠焦虑行为的治疗作用优于艾司西酞普兰组,其机制可能与外周促炎因子水平及海马脑区星形胶质细胞焦亡有关。Objective To study the antidepressant effect of Escitalopram combined with aerobic exercise on depression in mice and its mechanism. Methods C57 BL/6 male mice were used to establish a mouse model of depression by chronic unpredictable mild stress(CMS). The experiment was divided into control group(n=7), model group(n=7), Escitalopram group(n=7) and combined treatment group(Escitalopram+aerobic exercise group, n=7). Depressive behavior of mice was evaluated by sugar water preference test(SPT), forced swimming test(FST), tail suspension test(TST) and open field test(OFT). The levels of amino acids in hippocampus were measured by HPLC. The levels of inflammatory factors in peripheral blood of mice were detected by ELISA. The expression levels of GFAP and pyroptosis related proteins GSDMD, Caspase-1 in hippocampus were detected by immunofluorescence and Western blot. Results Compared with control group, SPT, the total route of OFT, and the expression of GFAP in the hippocampus were reduced in model group, the levels of pro-inflammatory factors in peripheral blood, taurine and γ-aminobutyric acid, GSDMD and cleaved-Caspase-1 in the hippocampus in model group were increased(all P<0.05). Compared with model group, SPT, the total route of OFT, and the expression of GFAP in the hippocampus were increased in Escitalopram group and combined treatment group, the levels of pro-inflammatory factors in peripheral blood, taurine and γ-aminobutyric acid, GSDMD and cleaved-Caspase-1 in the hippocampus in Escitalopram group and combined treatment group were reduced(all P<0.05). Compared with Escitalopram group, the total route of OFT was increased in combined treatment group(P<0.05), SPT and the expression of GFAP in the hippocampus showed a trend to increase, and the levels of pro-inflammatory factors in peripheral blood, taurine and γ-aminobutyric acid, GSDMD and cleaved-Caspase-1 in the hippocampus were decreased in combined treatment group, but there was no significant difference in these indexes between two groups(P>0.05).

关 键 词：抑郁症 艾司西酞普兰 有氧运动 炎症因子 胶质纤维酸性蛋白 焦亡 

分 类 号：R749[医药卫生—神经病学与精神病学]