目的:探讨8周自主跑轮运动对慢性不可预见性轻度应激(CUMS)大鼠抑郁样行为及外周神经内分泌因子生物节律表达的影响,从时间生物学方面探讨运动抗抑郁、促进脑康复的作用机制.方法:雄性SD大鼠90只,随机分为对照(control)组、模型(model)组及模型运动(model+exercise)组.采用CUMS方式建立抑郁模型,模型运动组前5周自愿跑轮,从第6周开始,附加21 d慢性复合应激,模型组于同一时点造模21 d.采用糖水偏好实验、旷场行为及高架十字迷宫系统观测大鼠焦虑情绪的行为学变化.行为学检测结束后第2天,连续24 h分6个时点(ZT1、ZT5、ZT9、ZT13、ZT17、ZT21)处死动物取血,每个时点处死5只大鼠,放射免疫法测定上述6个时点血清促肾上腺皮质激素(ACTH)含量,ELISA检测6个相同时点血清皮质酮(CORT)、褪黑素(MT)及血管活性肠肽(VIP)的含量,采用单一余弦法拟合曲线比较慢性应激大鼠各指标的节律周期、振幅、峰相位、中值的变化特点以及运动对其的影响.结果:与对照组相比,21 d的CUMS使模型组大鼠体重增加量明显减少(P<0.01),糖水消耗量明显降低(P<0.01);旷场实验中爬格数、直立次数及中央格停留时间均显著下降,而粪粒数明显增多(P<0.01);高架十字迷宫中开放臂停留时间的百分比和开放臂进入次数的百分比明显降低(P<0.01).运动对CUMS诱导的大鼠抑郁样行为有明显的改善作用.血浆近日节律输出肽及相关激素方面,慢性应激至抑郁样行为充分表达后,模型组大鼠血浆ACTH、CORT的相位与对照组完全相反,表现为时相的大幅度提前、含量波动幅度减小、昼夜分泌节律紊乱;MT的24 h分泌节律完全丧失且整体水平下降,表达量显著低于对照组;VIP虽仍存在24 h节律,但振幅明显低于对照组,峰相位也延迟6 h,表达量显著高于对照组.8周跑轮运动能显著改善应激大鼠的抑郁样行为及激素分泌量的异常,使血浆ACTH、MT、CORT和VIP的近日节律恢复正常.结论:运动可拮抗CUMS致大鼠的抑郁样行为,其作用机制可能与其在一定程度上能够调整外周神经内分泌激素的昼夜节律性和改变激素的分泌量有关.%AIM:To investigate the effect of 8-week middle intensity voluntary wheeling exercise on the de-pressive-like behavior and the circadian rhythmic alterations of plasma hormone and peptide induced by chronic unpredicta -ble mild stress (CUMS) in rats.METHODS: Male Sprague-Dawley rats (n =90) were randomly divided into model group, model+exercise group and control group .Rats in model+exercise group received 8-week voluntary wheel running exercise plus CUMS procedure during the last 3 weeks at the same time .Exploratory locomotor activity was assessed by open field test, the anxiety-like behavior was measured by elevated plus-maze test, and lack of pleasure was detected by su-crose preference test.Blood samples were collected at each of 6 time points (ZT1, 5, 9, 13, 17 and 21 on the 2nd day af-ter behavior testing ) .Plasma concentrations of corticosterone ( CORT) , melatonin ( MT) and vasoactive intestinal peptide ( VIP) were detected by ELISA .The plasma concentration of adrenocorticotropic hormone ( ACTH) was measured by ra-dioimmunoassay .The circadian rhythm changes of serum CORT , MT, VIP and ACTH concentrations in each group were compared by cosinor analysis .RESULTS:Compared with control group , locomotor activity , weight gain and sucrose con-sumption in model group were significantly reduced ( P<0.01 ) .The values of the percentage of open-arm time ( OT%) and open arm entries ( OE%) were obviously lower in model group than those in control group ( P<0.01 ) .Eight-week voluntary wheel running exercise may improve the above depression behavior caused by CUMS .The rats in model group showed an obvious disorder in circadian rhythm of plasma ACTH and CORT , including phase advance and decrease in am-plitude.There also showed a markedly blunted circadian rhythm and decreased level of plasma MT in model rats compared to control rats.VIP expression was significantly higher than that in control group with 24 h rhythm, but the amplitude was significantly lower than that in control group , peak phase also delayed for 6 h.Eight-week exercise significantly ameliorated the abnormal expression and the disturbance secretion rhythm of ACTH , CORT, MT and VIP in plasma .CONCLUSION:Eight-week voluntary wheeling exercise ameliorates CUMS-induced depressive-like behaviors probably by rescuing the dis-turbed circadian rhythms and abnormal secretion of these neuroendocrine factors .
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