蔡莉;李荣;吴清清;吴婷妮;
CAI Li1,LI Rong2*,WU Qing-qing2,WU Ting-ni2(1.Department of Pathology,Anhui Medical University,Hefei 230032,China; 2.College of Pharmacy,Anhui Medical University,Hefei 230032,China)

• 1:安徽医科大学病理学教研室
• 2:安徽医科大学药学院

摘要(Abstract)：

目的:观察橙皮苷对慢性应激抑郁模型大鼠行为学及下丘脑-垂体-肾上腺(HPA)轴的影响。方法:采用慢性轻度不可预见性应激(CUMS)制备大鼠抑郁模型,60只雄性SD大鼠随机分为正常组、模型组、橙皮苷(40,80,160 mg·kg-1)组及阳性药氟西汀(10 mg·kg-1)组。连续灌胃给药3周,糖水偏爱实验和强迫游泳实验测定动物行为学,检测血清皮质酮(CORT)、肾上腺指数、下丘脑促肾上腺皮质激素释放激素(CRF)mRNA以及下丘脑室旁核糖皮质激素受体(GR)蛋白,探讨橙皮苷的抗抑郁作用及机制。结果:与模型组相比,橙皮苷(40,80,160 mg·kg-1)治疗组大鼠的糖水消耗量均明显增加、强迫游泳不动时间有不同程度的减少。同时,橙皮苷能逆转CUMS大鼠过高的血清CORT水平和肾上腺指数,并能抑制CUMS大鼠下丘脑CRF mRNA表达、上调室旁核GR蛋白表达。结论:橙皮苷能有效改善CUMS大鼠行为学,表现出抗抑郁作用,其机制可能与调节HPA轴的功能有关。
Objective: To observe the effect of hesperidin on behavior and hypothalamic-pituitary-adrenal(HPA) axis of rat model of chronic stress-induced depression.Method: Chronic unpredictable mild stress(CUMS) was used to establish the rat depression model.Sixty male SD rats were divided randomly into six groups: the normal group,the model group,the hesperidin(40,80,160 mg·kg-1) group and the positive fluoxetine(10 mg·kg-1) group.They were orally administered with drugs for three weeks.The sucrose preference test and the forced swimming test(FST) were assayed to detect animal behavior.The levels of corticosterone(CORT) in serum,mRNA of corticotropin release factor(CRF) in hypothalamus as well as protein expression of glucocorticoid receptor(GR) in paraventricular nucleus(PVN) were determined to clarify the anti-depression effect and mechanism of hesperidin.Result: Compared with the model group,rats in the hesperidin(40,80,160 mg·kg-1) treatment group showed significant increase in the sucrose consumption and decrease in the immobility time in FST to varying degrees.Meanwhile,the excessively high serum CORT and adrenal index of CUMS rats were reversed by treatment with hesperidin.In addition,hesperidin inhibited CRF mRNA expression in hypothalamus and up-regulated GR protein expression in PVN among CUMS rats.Conclusion: Hesperidin could effectively improve the behavior of CUMS rats and show the anti-depression effet.Its mechanisms may be related to the function of regulating HPA axis.

关键词(KeyWords)： 橙皮苷;慢性轻度不可预见性应激;抗抑郁;下丘脑-垂体-肾上腺轴
hesperidin;chronic unpredictable mild stress;antidepressant;hypothalamic-pituitary-adrenal axis

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81201052);; 安徽省自然科学基金项目(1208085QH149);; 安徽省高校省级优秀青年人才基金项目(2009SQRZ041ZD);; 安徽医科大学博士科研基金项目(XJ201104)

作者(Authors): 蔡莉;李荣;吴清清;吴婷妮;
CAI Li1,LI Rong2*,WU Qing-qing2,WU Ting-ni2(1.Department of Pathology,Anhui Medical University,Hefei 230032,China; 2.College of Pharmacy,Anhui Medical University,Hefei 230032,China)

参考文献(References)：

• [1]郭秋平,高英,李卫民.百合皂苷对抑郁模型大鼠HPA轴的影响[J].中国药理学报,2010,26(5):699.
• [2]Zhang Z J.Therapeutic effects of herbal extracts and constituentsin animal models of psychiatric disorders[J].Life Sci,2004,75(14):1659.
• [3]Kawabata K,Kawai Y,Terao J.Suppressive effect of quercetinon acute stress-induced hypothalamic-pituitary-adrenal axis re-sponse in Wistar rats[J].J Nutr Biochem,2010,21(5):374.
• [4]Komori T,Fujiwara R,Tanida M,et al.Potential antidepressanteffects of lemon odor in rats[J].Eur Neuropsychopharmacol,1995,5(4):477.
• [5]Komiya M,Takeuchi T,Harada E.Lemon oil vapor causes ananti-stress effect via modulating the 5-HT and DA activities inmice[J].Behav Brain Res,2006,172(2):240.
• [6]Yi L T,Li J M,Li Y C,et al.Antidepressant-like behavioraland neurochemical effects of the citrus-associated chemical apige-nin[J].Life Sci,2008,82(13/14):741.
• [7]Herrera-Ruiz M,Zamilpa A,Gonzalez-Cortazar M,et al.Anti-depressant effect and pharmacological evaluation of standardizedextract of flavonoids from Byrsonima crassifolia[J].Phytomedi-cine,2011,18(14):1255.
• [8]Ito N,Nagai T,Yabe T,et al.Antidepressant-like activity of aKampo(Japanese herbal)medicine,Koso-san(Xiang-Su-San),and its mode of action via the hypothalamic-pituitary-adrenal axis[J].Phytomedicine,2006,13(9/10):658.
• [9]Chen X N,Meng Q Y,Bao A M,et al.The involvement of reti-noic acid receptor-alpha in corticotropin-releasing hormone geneexpression and affective disorders[J].Biol Psychiatry,2009,66(9):832.
• [10]Yang D,Li Q,Fang L,et al.Reduced neurogenesis and pre-synaptic dysfunction in the olfactory bulb of a rat model of depres-sion[J].Neuroscience,2011,192:609.
• [11]Guo J Y,Li C Y,Ruan Y P,et al.Chronic treatment with cele-coxib reverses chronic unpredictable stress-induced depressive-like behavior via reducing cyclooxygenase-2 expression in ratbrain[J].Eur J Pharmacol,2009,612(1/3):54.
• [12]Detke M J,Johnson J,Lucki I.Acute and chronic antidepressantdrug treatment in the rat forced swimming test model of depression[J].Exp Clin Psychopharmacol,1997,5(2):107.
• [13]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.
• [14]Swaab D F,Bao A M,Lucassen P J.The stress system in thehuman brain in depression and neurodegeneration[J].AgeingRes Rev,2005,4(2):141.
• [15]Binder E B,Nemeroff C B.The CRF system,stress,depressionand anxiety-insights from human genetic studies[J].Mol Psychi-atry,2010,15(6):574.
• [16]Bali B,Ferenczi S,Kovacs K J.Direct inhibitory effect of glu-cocorticoids on corticotrophin-releasing hormone gene expressionin neurones of the paraventricular nucleus in rat hypothalamic or-ganotypic cultures[J].J Neuroendocrinol,2008,20(9):1045.
• [17]Adcock I M,Barnes P J.Molecular mechanisms of corticosteroidresistance[J].Chest,2008,134(2):394.