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睡眠剥夺联合氟西汀对抑郁模型大鼠行为及血清促肾上腺皮质激素、皮质酮的影响
基金项目:浙江省医药卫生科技计划项目(2020KY747);浙江省杭州市科技发展计划重点专病专科项目(20150733Q 31);浙江省杭州市卫生科技计划项目(2018A49;2018A50)
摘    要:目的 探讨睡眠剥夺联合氟西汀对抑郁模型大鼠行为及血清促肾上腺皮质激素(ACTH)、皮质酮(CORT)的影响及可能的作用机制。方法 成年SD雄性大鼠60只,分为正常对照组(10只)和应激模型组(50只)。应激模型组进行21 d慢性轻度不可预见性应激(CMUS),行强迫游泳实验和蔗糖水消耗实验,随机分为抑郁组、氟西汀组、生理盐水组、睡眠剥夺组、睡眠剥夺+氟西汀组;分别予以单笼孤养、氟西汀灌胃、生理盐水灌胃、72 h快眼动睡眠剥夺、72 h快眼动睡眠剥夺联合氟西汀灌胃。28 d后再次行强迫游泳实验和蔗糖水消耗实验,并用ELISA法测定大鼠血清ACTH、CORT浓度。结果 应激后,应激模型组大鼠不动时间显著长于正常对照组,差异有统计学意义(P0.05),应激模型组大鼠蔗糖水消耗量、蔗糖水偏好显著低于正常对照组,差异有统计学意义(P0.05)。睡眠剥夺+氟西汀组大鼠强迫游泳不动时间比治疗前明显降低,差异有统计学意义(P0.05)。睡眠剥夺+氟西汀组大鼠蔗糖水消耗量、蔗糖水偏好较前显著升高,差异有统计学意义(P0.05)。治疗28 d后,氟西汀组、睡眠剥夺组及睡眠剥夺+氟西汀组ACTH、CORT水平显著低于抑郁组,差异有统计学意义(P0.05)。结论 睡眠剥夺联合氟西汀能够改善抑郁模型大鼠抑郁样行为,其机制可能与通过降低ACTH、CORT水平,降低HPA轴活性有关。

关 键 词:睡眠剥夺  氟西汀  抑郁  促肾上腺皮质激素  皮质酮

Effects of sleep deprivation combined with fluoxetine on behavior and serum adrenocorticotropic hormone and corticosterone in depression model rats
Abstract:Objective To investigate the effect of sleep deprivation combined with fluoxetine on behavior,serum a drenocorticotropic hormone(ACTH)and corticosterone(CORT)in depression model rats and its possible mechanism.Methods Sixty adult SD male rats were divided into the normal control group (10 rats) and the stress model group (50 rats).The stress model group underwent 21 days of chronic mild unpredictable stress (CMUS),forced swimming test and sucrose water consumption test.Afterwards,the rats were randomly divided into the depression group,the fluoxetine group,the normal saline group,the sleep deprivation group,and the sleep deprivation+fluoxetine group.They were given single cage,fluoxetine for gavage,normal saline for gavage,72-hour REM sleep deprivation,72-hour REM sleep deprivation combined with fluoxetine gavage,respectively.28 days later,forced swimming test and sucrose water consumption test were performed again,and the concentrations of ACTH and CORT in rat serum were determined by ELISA.Results After stress,the immobility time of rats was significantly longer in the stress model group than that in the normal control group,with statistically significant difference(P<0.05),and the sucrose water consumption and sucrose water preference of rats were significantly lower in the stress model group than those in the normal control group,with statistically significant differences (P<0.05).The forced swimming immobility time of rats was significantly lower in the sleep deprivation combined with fluoxetine group than that before treatment,and the difference was statistically significant(P<0.05).Sucrose water consumption and sucrose water preference were significantly higher in the sleep deprivation combined with fluoxetine group than before,and the differences were statistically significant (P<0.05).After 28 days of treatment,the levels of ACTH and CORT were significantly lower in the fluoxetine group,the sleep deprivation group and the sleep deprivation+fluoxetine group than those in the depression group,and the differences were statistically significant(P<0.05).Conclusion Sleep deprivation combined with fluoxetine can improve depressive behavior of depression model rats,and its mechanism may be related to the reduction of ACTH,CORT levels and HPA axis activity.
Keywords:Sleep deprivation  Fluoxetine  Depression  Adrenocorticotropic hormone  Corticosterone
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