目的 研究五味子甲素对慢性不可预知性温和刺激(chronic unpredicted mild stress, CUMS)诱导的大鼠抑郁样行为的影响及其作用机制初步探讨。方法 SD大鼠随机分为正常对照组、CUMS模型组、CUMS+氟西汀(10 mg·kg-1)组、CUMS+五味子甲素(25、50和100 mg·kg-1)组。采用CUMS法建立大鼠抑郁模型,造模后连续灌胃给药21 d。采用旷场实验、糖水偏爱实验、强迫游泳实验测试大鼠的抑郁样行为变化;ELISA法检测大鼠海马超氧化物歧化酶(superoxide dismutase, SOD)、过氧化氢酶(catalase,CAT)的活性及活性氧(reactive oxygen species, ROS)、前列腺素E2(PGE2)的含量。逆转录-聚合酶链反应(RT-PCR)法检测海马炎症因子白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α和IL-10的mRNA水平;Western blot法检测海马炎症因子IL-1β、TNF-α和IL-10含量的变化。结果 行为学结果显示,与正常对照组相比,模型组大鼠水平运动和垂直运动得分及糖水偏爱度均出现显著下降 (P<0.01),强迫游泳不动时间明显延长(P<0.01),给予五味子甲素后可以显著逆转糖水偏爱度的下降和强迫游泳不动时间的延长;生化检测结果显示,模型组大鼠海马ROS和PGE2含量显著升高 (P<0.01),SOD和CAT的活性显著降低 (P<0.01),IL-1β、TNF-α和IL-10 mRNA和蛋白水平明显升高 (P<0.05或P<0.01)。结论 五味子甲素和氟西汀均能不同程度地改善CUMS诱导的上述改变。五味子甲素能明显改善CUMS引起的大鼠抑郁样行为,其作用机制可能与缓解海马氧化应激水平和炎症反应相关。
Abstract
OBJECTIVE To investigate the anti-depressant effect of schisandrin A in rats with depression caused by chronic unpredictable mild stress(CUMS)as well as the relevant mechanism. METHODS The depression-like rat model using CUMS was established. Rats were randomly divided into control, CUMS model, CUMS+fluoxetine (10 mg·kg-1)and CUMS + schisandrin A (25, 50, 100 mg·kg-1)groups. Drugs or vehicle were administrated after stress procedures for 21 d. Open-field test (OFT), sucrose preference tests (SPT)and forced swim test (FST)were used to evaluate the anti-depressant effects of schisandrin A. The reactive oxygen species (ROS)and prostaglandin E2 (PGE2) level as well as superoxide dismutase (SOD) and catalase (CAT)activities in hippocampus were determined by ELISA methods. IL-1β, TNF-α, and IL-10 expression were measured by real time qPCR and Western blot analysis. RESULTS Behavioral test indicated that crossing score and rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than control group (P<0.01), while immobility time in FST was significantly increased (P<0.01). Compared with those in control group, the ROS and PGE2 level increased significantly (P<0.01), SOD and CAT activities decreased significantly (P< 0.01),the mRNA and protein level of IL-1β, TNF-α, and IL-10 were increased significantly (P<0.05 or P<0.01)in rats of CUMS. CONCLUSION Schisandrin A and fluoxetine could ameliorate those changes induced by CUMS. Schisandrin A could improve the depression-like behaviors of rats induced by CUMS, of which the mechanism might involve the antioxidant and anti-inflammatory effects.
关键词
五味子甲素 /
抑郁 /
抗氧化应激 /
抗炎
{{custom_keyword}} /
Key words
schisandrin A /
depression /
antioxidant /
anti-inflammatory
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] KESSLER R C, BROMET E J. The epidemiology of depression across cultures[J].Annu Rev Public Health, 2013, 34(1):119-138.
[2] BROMET E, ANDRADE L H, HWANG I, et al. Cross-national epidemiology of DSM-Ⅳ major depressive episode[J].BMC Med, 2011, 9: 90.
[3] KIECOLT-GLASER J K, FAGUNDES C P, ANDRIDGE R, et al. Depression, daily stressors and inflammatory responses to high-fat meals: when stress overrides healthier food choices[J]. Mol Psychiatry, 2017, 22(3):476-482.
[4] FERGUSON E H, DI FLORIO A, PEARSON B, et al. HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression[J]. Arch Womens Ment Health, 2017, 20(3):411-420.
[5] Ch.P(2015)Vol Ⅰ(中国药典2015年版. 一部)[S].2015:66-67.
[6] GU W, WEI N, WANG Z. LC Analysis of lignans from Schisandra sphenanthera Rehd. et Wils[J]. Chromatographia, 2008, 67(11-12):979-983.
[7] KIM H M, RYU B, LEE J S, et al. Schisandrosides A-D, dibenzocyclooctadiene lignan glucosides from the roots of Schisandra chinensis[J]. Chem Pharm Bull(Tokyo), 2015, 63(9):746-751.
[8] YANG Q, QU X B, LI H, et al. Schisandra chemical composition and pharmacological action research[J]. Jilin J Tradit Chin Med(吉林中医药), 2015,35(6):626-628.
[9] YAN T, HE B, WAN S, et al. Antidepressant-like effects and cognitive enhancement of Schisandra chinensis in chronic unpredictable mild stress mice and its related mechanism[J].Sci Rep, 2017, 7(1):6903.
[10] JING R, LI H F, CHENG Y G, et al. Improvement of Schisandrae Fructus processed products on depressive mice induced by chronic unpredictable mild stress[J]. Drugs Clin(现代药物与临床), 2016(11):1698-1702.
[11] XU F M. Antidepressant effects and mechanisms of Schisandra chinensis and related compound medicine JWYQS[D]. Nanning: Guangxi Medical University, 2017.
[12] JEONG E J, LEE H K, LEE K Y, et al. The effects of lignan-riched extract of Shisandra chinensis on amyloid-beta-induced cognitive impairment and neurotoxicity in the cortex and hippocampus of mouse[J].J Ethnopharmacol, 2013, 146(1):347-354.
[13] DENG Z Y, YUAN Y P, LÜ L F. Effect of ganoderma spore oil on behavior in depression mice and its neurophysiology mechanisms[J]. Chin Pharm J(中国药学杂志), 2017,52(15):1325-1330.
[14] WILLNER P, TOWELL A, SAMPSON D, et al. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant[J].Psychopharmacology (Berl), 1987, 93(3):358-364.
[15] GENTIL L, VASILIADIS H M, BERBICHE D, et al. Impact of depression and anxiety disorders on adherence to oral hypoglycemics in older adults with diabetes mellitus in Canada[J].Eur J Ageing, 2017, 14(2):111-121.
[16] JACOBS J M, TRAEGER L, EUSEBIO J, et al. Depression, inflammation, and epidermal growth factor receptor (EGFR)status in metastatic non-small cell lung cancer: a pilot study[J].J Psychosom Res, 2017, 99: 28-33.
[17] SARFO F S, JENKINS C, SINGH A, et al. Post-stroke depression in Ghana: Characteristics and correlates[J]. Neurol Sci, 2017, 379: 261-265.
[18] CATENA-DELL'OSSO M, BELLANTUONO C, CONSOLI G, et al. Inflammatory and neurodegenerative pathways in depression: a new avenue for antidepressant development?[J].Curr Med Chem, 2011, 18(2):245-255.
[19] LI M, LI C, YU H, et al. Lentivirus-mediated interleukin-1beta (IL-1beta)knock-down in the hippocampus alleviates lipopolysaccharide (LPS)-induced memory deficits and anxiety-and depression-like behaviors in mice[J].J Neuroinflam, 2017, 14(1):190.
[20] DEYAMA S, SHIMODA K, SUZUKI H, et al. Resolvin E1/E2 ameliorate lipopolysaccharide-induced depression-like behaviors via ChemR23[J].Psychopharmacology (Berl), 2018, 235(1):329-336.
[21] CHANG Y, HSIEH C Y, PENG Z A, et al. Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats[J].J Biomed Sci, 2009, 16:9.
[22] YANG D F, LIU Z H, CHEN Y F, et al. Effect of schisandrin A on the expression of inflammatory mediators in mononuclear macrophages[J]. Chin J Gerontol(中国老年学杂志), 2013,33(23):5911-5913.
[23] LI Y, ZHAO Y Y, TONG Z L, et al. Investigation of SchA on apoptosis of SH-SY5Y cells induced by MPP[J]. J Toxicol(毒理学杂志), 2017,31(2):98-101.
[24] LI Y, ZHANG W, CAI T J, et al. Study on the effect of Sch A to ERK signal pathway in MPP~+-treated SH-SY5Y cells[J]. Chin Veter J(中国兽医杂志), 2017,53(8):50-52.
[25] BOUVIER E, BROUILLARD F, MOLET J, et al. Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression[J]. Mol Psych, 2017, 22(12):1701-1713.
[26] KOTAN V O, SARANDOL E, KIRHAN E, et al. Effects of long-term antidepressant treatment on oxidative status in major depressive disorder: a 24-week follow-up study[J].Prog Neuropsychopharmacol Biol Psychiatry, 2011, 35(5):1284-1290.
[27] TAO W, DONG Y, SU Q, et al. Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway[J].Behav Brain Res, 2016, 308: 177-186.
[28] ZHOU S Y, DENG Z R, TAN L, et al. Protection effect of schisanhenol on learning and memory acquired disorder induced by scopolamine in mice[J]. Chin Pharm J(中国药学杂志), 2014, 49(23):2088-2091.
[29] ZHANG W F, YANG Y, SU X, et al. Deoxyschizandrin suppresses dss-induced ulcerative colitis in mice[J].Saud J Gastroenterol, 2016, 22(6):448-455.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
广东省医学科学技术研究基金资助(A2016557)
{{custom_fund}}
PDF(3008 KB)
