绿萼梅总黄酮对慢性应激抑郁模型大鼠抑郁行为的影响及机制研究
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摘要
目的:考察绿萼梅总黄酮对慢性应激抑郁模型大鼠抑郁行为的影响及机制。方法:将60只大鼠随机分为生理盐水组、模型组、氟西汀组(阳性对照,20 mg/kg)和绿萼梅总黄酮低、中、高剂量组(80、160、240 mg/kg),每组10只。除生理盐水组外,其余各组大鼠均采用慢性不可预见性温和应激(CUMS)+孤养法复制抑郁模型,并于造模同时ig相应药物,每天1次,连续28 d。观察大鼠体质量、摄食量的变化及糖水偏爱程度;通过强迫游泳实验、悬尾实验测定大鼠不动时间以及旷场实验测定大鼠中央格停留时间、水平穿越格数、站立次数、修饰次数的变化;并测定末次给药24 h后大鼠血清中肿瘤坏死因子α(TNF-α)、皮质醇、白细胞介素6(IL-6)、5-羟色胺(5-HT)水平。结果:与生理盐水组比较,模型组大鼠的体质量增加值、摄食量、糖水偏爱百分比均降低;强迫游泳和悬尾实验的不动时间延长;旷场实验的中央格停留时间延长、水平穿越格数、站立次数、修饰次数均减少;血清中TNF-α、皮质醇水平升高,IL-6、5-HT水平降低,差异均有统计学意义(P<0.05或P<0.01)。与模型组比较,除绿萼梅总黄酮低剂量组大鼠糖水偏爱百分比、强迫游泳不动时间、旷场实验修饰次数以及绿萼梅总黄酮低、中剂量组大鼠血清中IL-6、5-HT水平改善不明显外,其余各给药组大鼠上述指标均明显改善(P<0.05或P<0.01)。结论:绿萼梅总黄酮能明显改善CUMS诱导的大鼠抑郁行为,其机制可能与抑制炎症反应、调节下丘脑-垂体-肾上腺轴功能有关。
OBJECTIVE:To investigate the effects and mechanism of total flavonoids from Armeniaca mume on depression in chronic stress depression model rats. METHODS:60 rats were randomly divided into normal saline group,model group,fluoxetine group(positive control,20 mg/kg)and total flavonoids from A. mume low-dose,medium-dose,high-dose groups(80,160,240 mg/kg),10 in each group. Except for normal saline group,the other groups adopted chronic unpredictable mild stress(CUMS)+solitary feeding condition to induce depression model. These groups were intragastrically administered,once a day,for28 d. Changes of body mass and food intake,degree of preference for sugar were observed;forced swimming test and tail suspension test were used to determine the time that rats did not move;open field test was used to determine the changes of residence time in central square,horizontal crossing lattice,standing times,modification times;tumor necrosis factor α(TNF-α),cortisol,interleukin 6(IL-6),serotonin(5-HT)levels in serum after 24 h of last administration were determined. RESULTS:Compared with normal saline group,growth of body mass,food intake and sugar preference percentage in model group were decreased;the time that rats did not move was prolonged in forced swimming test and tail suspension test;residence time in central square was prolonged,while horizontal crossing lattice,standing times and modification times were decreased in open field test;serum levels of TNF-α,cortisol were increased,while IL-6,5-HT were decreased,with statistical significances(P<0.05 or P<0.01). Compared with model group,except that there were no obvious improvement in sugar preference percentage,the time that rats did not move in forced swimming test,modification times in open field test in total flavonoids from A. mume low-dose group and IL-6,5-HT levels in serum in total flavonoids from A. mume low-dose,medium-dose groups,the above-mentioned indexes were obviously improved in other groups(P<0.05 or P<0.01). CONCLUSIONS:Total flavonoids from A. mume can obviously improve the CUMS-induced depression in rats,and the mechanism may be related to inhibiting inflammation response,adjusting the hypothalamus-pituitary-adrenal axis functions.
OBJECTIVE:To investigate the effects and mechanism of total flavonoids from Armeniaca mume on depression in chronic stress depression model rats. METHODS:60 rats were randomly divided into normal saline group,model group,fluoxetine group(positive control,20 mg/kg)and total flavonoids from A. mume low-dose,medium-dose,high-dose groups(80,160,240 mg/kg),10 in each group. Except for normal saline group,the other groups adopted chronic unpredictable mild stress(CUMS)+solitary feeding condition to induce depression model. These groups were intragastrically administered,once a day,for28 d. Changes of body mass and food intake,degree of preference for sugar were observed;forced swimming test and tail suspension test were used to determine the time that rats did not move;open field test was used to determine the changes of residence time in central square,horizontal crossing lattice,standing times,modification times;tumor necrosis factor α(TNF-α),cortisol,interleukin 6(IL-6),serotonin(5-HT)levels in serum after 24 h of last administration were determined. RESULTS:Compared with normal saline group,growth of body mass,food intake and sugar preference percentage in model group were decreased;the time that rats did not move was prolonged in forced swimming test and tail suspension test;residence time in central square was prolonged,while horizontal crossing lattice,standing times and modification times were decreased in open field test;serum levels of TNF-α,cortisol were increased,while IL-6,5-HT were decreased,with statistical significances(P<0.05 or P<0.01). Compared with model group,except that there were no obvious improvement in sugar preference percentage,the time that rats did not move in forced swimming test,modification times in open field test in total flavonoids from A. mume low-dose group and IL-6,5-HT levels in serum in total flavonoids from A. mume low-dose,medium-dose groups,the above-mentioned indexes were obviously improved in other groups(P<0.05 or P<0.01). CONCLUSIONS:Total flavonoids from A. mume can obviously improve the CUMS-induced depression in rats,and the mechanism may be related to inhibiting inflammation response,adjusting the hypothalamus-pituitary-adrenal axis functions.
引文
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[17]Koo JW,Duman RS.IL-1 beta is an essential mediator of the antineurogenic and anhedonic effects of stress[J].Proc Natl Acad Sci USA,2008,105(2):751-756.
[2]Yang D,Li Q,Fang L,et al.Reduced neurogenesis and pr esynaptic dysfunction in the olfactory bulb of a rat mode of depression[J].Neuroscience,2011,192(1):609-618.
[3]江苏新医学院.中药大辞典:上册[M].上海:上海科学技术出版社,1997:735.
[4]刘秋琼,林秋晓,谭淑敏,等.慢性温和不可预知应激模型大鼠血浆中正五聚蛋白3的质量浓度变化及舍曲林的干预作用研究[J].中国药房,2013,24(41):3858-3860.
[5]杨小莹,马世平,瞿融.柴胡提取物对慢性应激抑郁大鼠脂质过氧化及淋巴细胞增殖的影响[J].中国药科大学学报,2007,38(5):442-445.
[6]Sun J,Wang F,Hong GL,et al.Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress[J].Neurosci Lett,2016,doi:10.1016/j.neulet.2016.03.003.
[7]匡胜男,罗映,田小燕,等.美洛昔康改善慢性应激大鼠抑郁行为的机制初探[J].中国药理学通报,2016,32(2):263-268.
[8]于红,郭蕾,柴金苗,等.逍遥散对肝郁证大鼠治疗作用的实验研究[J].辽宁中医杂志,2014,41(11):2485-2487.
[9]Kinn AM,Grnli J,Fiske E,et al.A double exposure to social defeat induces sub-chronic effects on sleep and open field behaviour in rats[J].Physiol Behav,2008,95(4):553-561.
[10]刘丽琴,罗艳,张瑞睿,等.人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响[J].中国中药杂志,2011,36(10):1342-1347.
[11]付红勇,王星华,殷盛明,等.抑郁症分子机制中5-羟色胺2C受体的作用[J].生理科学进展,2014,12(3):221-224.
[12]黄满丽,许毅.抑郁症与细胞因子的研究进展[J].国际精神病学杂志,2012,39(1):14-17.
[13]韦云龙,农玉贤,潘江艳,等.舍曲林辅助治疗对抑郁症合并冠心病患者血清炎症因子水平及预后的影响[J].现代生物医学进展,2014,14(4):752-754.
[14]Sara PP,Carolina V,Matias M,et al.How are neuroticism and depression related to the psychophysiological stress response to acute stress in healthy older people[J].Physiol Behav,2016,doi:10.1016/j.physbeh.2016.01.015.
[15]Doane LD,Franz CE,Prom-Wormley E,et al.Negative emotionality,depressive symptoms and cortisol diurnal rhythms:analysis of a community sample of middle-aged males[J].Horm Behav,2011,60(2):202-209.
[16]Dziurkowska E,Wesolowski M.Salivary cortisol in women with major depressive disorder under selective serotonin reuptake inhibitors therapy[J].Arch Womens Ment Health,2013,16(2):139-147.
[17]Koo JW,Duman RS.IL-1 beta is an essential mediator of the antineurogenic and anhedonic effects of stress[J].Proc Natl Acad Sci USA,2008,105(2):751-756.