慢性应激和脂多糖构建昆明种小鼠抑郁症动物模型  

Establishment of depression model induced by chronic stress and lipopolysaccharide in Kunming mice

作　　者：张露文 唐文娟 李瑞瑞 于海玲[1] ZHANG Luwen;TANG Wenjuan;LI Ruirui;YU Hailing(Faculty of Medicine,Yanbian University,Yanji 133000,China)

机构地区：[1]延边大学医学院,吉林延吉133000

出　　处：《沈阳药科大学学报》2022年第1期30-39,共10页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金地区科学基金项目(81760650,81960656)。

摘　　要：目的利用慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)联合脂多糖(lipopolysaccharide,LPS)构建稳定的抑郁症动物模型。方法雄性昆明种小鼠48只分为正常对照组、LPS组(LPS 0.2 mg·kg^(-1),i.p.)、CUMS组(CUMS+生理盐水10 mL·kg^(-1),i.p.)、CUMS+LPS组(CUMS+LPS 0.2 mg·kg^(-1),i.p.)。CUMS处理第14天、21天、28天及第18天、25天、32天,除正常对照组外,其余3组均依据分组进行腹腔注射LPS或相应溶剂。LPS或生理盐水注射后24 h进行相关行为学指标检测。最后一次行为学指标检测结束后,取脑组织,酶联免疫吸附法检测小鼠白细胞介素6(interleukin 6,IL-6)和白细胞介素10(interleukin 10,IL-10)水平,硫代巴比妥酸法检测丙二醛(malondialdehyde,MDA)水平,黄嘌呤氧化酶法测定总超氧化物歧化酶(total superoxide dismutase,T-SOD)活力,分光光度法检测总抗氧化能力(total antioxidant capacity,T-AOC)水平。结果在实验第29~33天,与正常对照组相比,CUMS组、LPS组、CUMS+LPS组,在旷场实验(open field test,OFT)中,小鼠的运动时间、运动距离均显著降低;在高架十字迷宫实验(elevated plus maze,EPM)中,开臂探索时间均显著降低、闭臂滞留时间均显著延长;在强迫游泳(forced swimming test,FST)和悬尾实验(tail suspension test,TST)中,累积不动时间均显著升高;蔗糖偏好实验(sucrose preference test,SPT)中的蔗糖偏好率均显著降低。小鼠脑组织中炎症因子IL-6含量均升高、IL-10含量均降低;氧化应激指标中T-SOD含量均显著降低;而且,CUMS+LPS组,在OFT中的中央区停留时间、周边区停留时间、站立次数均缩短,角落滞留时间延长;在EPM中的开臂探索距离显著降低、闭臂滞留距离延长;脑组织T-AOC水平显著下降、MDA含量显著升高。此外,与CUMS组或LPS组相比,CUMS+LPS组在OFT中的运动时间均缩短,在EPM中的开臂滞留时间和开臂运动距离百分比降低、闭臂滞留时间和闭臂运动距离百分Objective To establish a more stable animal model of depression by chronic unpredictable mild stress(CUMS)and lipopolysaccharide(LPS).Methods Forty-eight male Kunming mice were divided into four groups:normal control group,LPS group(0.2 mg·kg^(-1),i.p.),CUMS group(CUMS+saline 10 mL·kg^(-1),i.p.)and CUMS+LPS group(0.2 mg·kg^(-1),i.p.).CUMS+LPS group and CUMS group were given chronic stress stimulation to establish CUMS model,while the normal control group and LPS group were given water without any additional stimulation.On the 14 th,21 th,28 th and 18 th,25 th and 32 th days,the other three groups were injected with LPS or corresponding solvent,except for the normal control group.The relevant behavioral parameters were detected at 24 hours after injection of LPS.After the last behavioral indicator test,the brain tissue was taken,the levels of IL-6 and IL-10 were detected by enzyme linked immunosorbent assay,the levels of malondialdehyde(MDA)were detected by thiobarbituric acid assay,and the total superoxide dismutase activity(T-SOD)and total antioxidant capacity(T-AOC)level were detected by xanthine oxidase method and spectrophotometric method,respectively.Results Compared with normal control group,for the mice in CUMS group,LPS group,and CUMS+LPS group,the movement time and distance of mice were significantly reduced in the open field test(OFT);in the elevated plus maze test(EPM),the time spent in open arms were significantly reduced,and the time spent in closed arm were significantly increased;in forced swimming test(FST)and tail suspension test(TST),the accumulated immobility time significantly increased;and the sucrose preference rate decreased in the sucrose preference test(SPT);and the contents of IL-6 were significantly increased,while the contents of IL-10 obviously reduced;and T-SOD were decreased significantly in brain tissue of mice.Furthermore,for the mice in CUMS+LPS group,the retention time in central domain,the retention time in four sides and the times of rearing were all decreased,while the cor

关 键 词：慢性不可预见性温和应激 脂多糖 抑郁症模型 昆明种小鼠 

分 类 号：R96[医药卫生—药理学]