基于~1H-NMR代谢组学复方柴归方干预抑郁模型大鼠血清代谢物规律分析
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摘要
目的采用~1H-NMR代谢组学方法分析复方柴归方干预抑郁模型大鼠血清代谢物组的变化规律。方法采用慢性温和不可预知应激(CUMS)程序对大鼠进行造模,以复方柴归方及阳性药(文拉法辛)为干预药物,采用核磁共振方法对大鼠血清进行分析,数据预处理后导入SIMCA-P 14.1软件进行多元统计分析,从小分子代谢物角度对复方柴归方的抗抑郁药效进行验证,并寻找出潜在的疾病生物标志物和药物疗效标志物。结果 CUMS抑郁大鼠模型复制成功,代谢组学结果表明与模型组相比,CUMS抑郁大鼠经阳性药和复方柴归方干预后血清中异亮氨酸、氧化三甲胺和肌酸水平升高,N-乙酰糖蛋白、胆碱和葡萄糖水平降低,差异显著(P<0.05、0.01)。结论复方柴归方干预后CUMS模型大鼠血清差异代谢物水平明显回调,该研究可为复方柴归方抗抑郁作用机制研究提供参考依据。
Objective To analyze the effect of Compound Chaigui Prescription on the changes of serum metabolites in rats with depression by ~1H-NMR metabolomics. Methods Rats model established were modeled by chronic mild unpredictable stress(CUMS) procedure. Compound Chaigui Prescription and positive drugs(venlafaxine) were used as intervention drugs. Rat serum was analyzed by nuclear magnetic resonance(NMR) method. After data pretreatment, SIMCA-P 14.1 software was introduced for multivariate statistical analysis to verify the antidepressant efficacy of Compound Chaigui Prescription from the perspective of small molecule metabolites, and find potential disease biomarkers and drug efficacy markers. Results The CUMS depression rat model was successfully replicated. The metabolomics results showed that the levels of isoleucine, trimethylamine oxide, and creatine in the serum of CUMS-depressed rats were significantly higher than those of the model group. The levels of N-acetyl-glycoprotein, choline, and glucose were decreased with a significant difference(P < 0.05, 0.01). Conclusion The serum metabolite levels in CUMS model rats were significantly corrected after Compound Chaigui Prescription intervention. This study can provide reference for the study of antidepression mechanism of Compound Chaigui Prescription.
Objective To analyze the effect of Compound Chaigui Prescription on the changes of serum metabolites in rats with depression by ~1H-NMR metabolomics. Methods Rats model established were modeled by chronic mild unpredictable stress(CUMS) procedure. Compound Chaigui Prescription and positive drugs(venlafaxine) were used as intervention drugs. Rat serum was analyzed by nuclear magnetic resonance(NMR) method. After data pretreatment, SIMCA-P 14.1 software was introduced for multivariate statistical analysis to verify the antidepressant efficacy of Compound Chaigui Prescription from the perspective of small molecule metabolites, and find potential disease biomarkers and drug efficacy markers. Results The CUMS depression rat model was successfully replicated. The metabolomics results showed that the levels of isoleucine, trimethylamine oxide, and creatine in the serum of CUMS-depressed rats were significantly higher than those of the model group. The levels of N-acetyl-glycoprotein, choline, and glucose were decreased with a significant difference(P < 0.05, 0.01). Conclusion The serum metabolite levels in CUMS model rats were significantly corrected after Compound Chaigui Prescription intervention. This study can provide reference for the study of antidepression mechanism of Compound Chaigui Prescription.
引文
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[26]Sahlin K,Tonkonogi M,S?derlund K.Energy supply and muscle fatigue in humans[J].Acta Physiol,1998,162(3):261-266.
[2]Thwala J D,Sherwood P M,Edwards S D.Description of philophonetics counselling as expressive therapeutic modality for treating depression[J].Ai Society,2018(3):1-6.
[3]Nicholson J K,Lindon J C,Holmes E.“Metabonomics”:Understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J].Xenbiotica,1999,29(11):1181-1189.
[4]陈佳佳,李爱平,张晓琴,等.基于核磁共振代谢组学的成分数据分析在中药评价中的应用[J].中草药,2016,47(19):3522-3526.
[5]李媛,张雯霞,何盼,等.基于1H-NMR代谢组学的还贝止咳方对咳嗽变异性哮喘豚鼠的干预作用[J].中草药,2018,49(10):2230-2239.
[6]赵珊,王鹏程,冯健,等.代谢组学技术及其在中医药研究中的应用[J].中草药,2015,46(5):756-765.
[7]Zhang P J,Li Y M,Zhang Y N,et al.Application and prospect of toxicity quality markers of traditional Chinese medicine based on metabolomics[J].Chin Herb Med,2018,10(2):108-115.
[8]Mao Q,Xu J D,Kong M,et al.LC-MS-based metabolomics in traditional Chinese medicines research:Personal experiences[J].Chin Herb Med,2017,9(1):14-21.
[9]郭慧,崔扬,王秋红,等.基于代谢组学技术的中药复方研究近况[J].中国实验方剂学杂志,2017,23(1):213-219.
[10]张涛,赵芳,张潇,等.复方柴归方抗抑郁作用及其调控5-羟色胺代谢途径机制研究[J].中草药,2018,49(6):1338-1344.
[11]Banerjee P,Dutta M,Srivastava S,et al.1H-NMR serum metabonomics for understanding metabolic dysregulation in women with idiopathic recurrent spontaneous miscarriage during implantation window[J].J Proteome Res,2014,13(6):3100-3106.
[12]Diao C,Zhao L,Guan M,et al.Systemic and characteristic metabolites in the serum of streptozotocin-induced diabetic rats at different stages as revealed by a 1H-NMR based metabonomic approach[J].Mol Biosyst,2014,10(3):686-693.
[13]李金兵,李翼鹏,田俊生,等.基于慢性温和不可预知应激模型内源性代谢物变化探讨抑郁症病理机制[J].中草药,2013,44(1):108-115.
[14]Shimomura Y,Harris R A.Metabolism and physiological function of branched-chain amino acids:Discussion of session 1[J].J Nutr,2006,doi:10.1093/jn/136.1.232S.
[15]Zheng S,Zhang S,Yu M,et al.An 1H-NMR and UPLC-MS-based plasma metabonomic study to investigate the biochemical changes in chronic unpredictable mild stress model of depression[J].Metabolomics,2011,7(3):413-423.
[16]王伟明,黄育华,熊振芳,等.肝气郁结证大鼠尿液代谢组学研究[J].中西医结合肝病杂志,2010,20(2):102-105.
[17]Furukawahibi Y,Nitta A,Ikeda T,et al.The hydrophobic dipeptide Leu-Ile inhibits immobility induced by repeated forced swimming via the induction of BDNF[J].Behav Brain Res,2011,220(2):271-280.
[18]Eaton W W,Armenian H,Gallo J,et al.Depression and risk for onset of type II diabetes:A prospective population-based study[J].Diabetes Care,1996,19(10):1097-1102.
[19]李则挚,张晨,方贻儒.线粒体功能异常假说在抑郁症中的研究进展[J].中华精神科杂志,2012,45(3):181-184.
[20]Cao X,Li L P,Wang Q,et al.Astrocyte-derived ATPmodulates depressive-like behaviors[J].Nat Med,2013,19(1):773-777.
[21]Maes M,Delange J,Ranjan R,et al.Acute phase proteins in schizophrenia,mania and major depression:Modulation by psychotropic drugs[J].Psych Res,1997,66(1):1-11.
[22]王冬青,朱彦,李月峰,等.首发抑郁症患者敏感脑结构的磁共振质子波谱分析[J].中华行为医学与脑科学杂志,2011,20(1):19-21.
[23]Dinan T G,Cryan J F.Regulation of the stress response by the gut microbiota:Implications for psychoneuroendocrinology[J].Psychoneuroendocrinology,2012,37(9):1369-1378.
[24]Bercik P,Denou E,Collins J,et al.The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice[J].Gastroenterology,2011,141(2):599-609.
[25]夏小涛,孙宁,刘彩春,等.基于1H-NMR代谢组学的抑郁症生物标志物发现及帕罗西汀干预作用[J].药学学报,2016,51(4):595-599.
[26]Sahlin K,Tonkonogi M,S?derlund K.Energy supply and muscle fatigue in humans[J].Acta Physiol,1998,162(3):261-266.