葶苈子对肾阴虚水肿模型干预作用的代谢组学研究
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摘要
目的:运用代谢组学方法研究肾阴虚水肿大鼠尿液代谢组学的变化及葶苈子的干预作用。方法:通过UPLC-Q-TOF-MS检测各组大鼠尿液中代谢产物的变化;运用主成分分析(PCA)、正交偏最小二乘判别分析(OPLSDA)等方法分析和筛选潜在生物标志物;应用MeV软件对生物标志物进行热度图绘制和聚类分析。结果:由40个与模型相关的生物标志物富集得到了4条显著受到干扰的代谢途径:苯丙氨酸、色氨酸、组氨酸和嘧啶代谢途径。经葶苈子干预后,模型大鼠体内多数生物标志物的水平被回调至正常水平,代谢紊乱得以纠正。结论:代谢组学可从整体代谢水平上阐释肾阴虚水肿模型以及葶苈子对其干预机制,为中医证候和中药作用机制研究提供了一种新的研究思路和方法。
Objective: To research the kidney yin deficiency edema and to assess the integral efficacy of Descurinia sophia seeds in rat model by metabonomics. Methods: UPLC-Q-TOF-MS method was used to detect the changes of urine metabolites in all groups. Principal component analysis( PCA) and Orthogonal partial least squares discriminant analysis( OPLS-DA) were utilized to analyze and screen potential biomarkers. MeV software was adopted for heat map drawing and cluster analysis. Results: 40 biomarkers which identified were mainly related to four metabolic pathways that were significantly disrupted( Phenylalanine,Tryptophan,Histidine and Pyrimidine). The mostly biomarker levels in the seeds of Descurinia sophia group exhibited a reverse to normal status,metabolic disorders can be corrected. Conclusion: Metabolomics describes the pathological status of kidney yin deficiency edema and the effect of the seeds of Descurinia sophia from an overall level,which provides a powerful approach for illustrating the Chinese medicine syndrome and action mechanism of Chinese herbal medicine.
Objective: To research the kidney yin deficiency edema and to assess the integral efficacy of Descurinia sophia seeds in rat model by metabonomics. Methods: UPLC-Q-TOF-MS method was used to detect the changes of urine metabolites in all groups. Principal component analysis( PCA) and Orthogonal partial least squares discriminant analysis( OPLS-DA) were utilized to analyze and screen potential biomarkers. MeV software was adopted for heat map drawing and cluster analysis. Results: 40 biomarkers which identified were mainly related to four metabolic pathways that were significantly disrupted( Phenylalanine,Tryptophan,Histidine and Pyrimidine). The mostly biomarker levels in the seeds of Descurinia sophia group exhibited a reverse to normal status,metabolic disorders can be corrected. Conclusion: Metabolomics describes the pathological status of kidney yin deficiency edema and the effect of the seeds of Descurinia sophia from an overall level,which provides a powerful approach for illustrating the Chinese medicine syndrome and action mechanism of Chinese herbal medicine.
引文
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[2]郭继光,白杨,周广滨.阿霉素肾病动物模型的研究进展[J].江苏大学学报(医学版),2014,24(2):181-184.
[3]杜江,李楠,王和鸣.肾虚模型造模方法及相关指标[J].中国组织工程研究与临床康复,2010,14(50):9433-9436.
[4]任真真,伦立德,李新伦,等.慢性肾脏病3~5期患者肾功能与蛋白结合类毒素相关性研究[J].军事医学,2015,39(7):532-549.
[5]Patel KP,Luo FJ,Plummer NS,et al.The production of pcresol sulfate and indoxyl sulfate in vegetarians versus omnivores[J].Clin J Am Soc Nephrol,2012,7(6):982-988.
[6]Winchester JF,Hostetter TH,Meyer TW.p-Cresol sulfate:further understanding of its cardiovascular disease potential in CKD[J].Am J Kidney Dis,2009,54(5):792-794.
[7]Sun CY,Hsu HH,Wu MS.p-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene expressions in cultured proximal renal tubular cells[J].Nephrol Dial Transplant,2013,28(1):70-78.
[8]Wang L,Cao AL,Chi YF,et al.You-gui Pill ameliorates renal tubulointerstitial fibrosis via inhibition of TGF-β/Smad signaling pathway[J].J Ethnopharmacol,2015,169(1):229-238.
[9]Zhang W,Wang W,Yu H,et al.Interleukin 6 underlies angiotensinⅡ-induced hypertension and chronic renal damage[J].Hypertension,2012,59(1):136-144.
[10]Barker SL,Pastor J,Carranza D,et al.The demonstration ofαKlotho deficiency in human chronic kidney disease with a novel synthetic antibody[J].Nephrol Dial Transplant,2015,30(2):223-233.
[11]于冲,马梦彪,夏海华,等.色氨酸代谢和应用前景展望[J].黑龙江科学,2014,5(5):36-37.
[12]孔红,朱鼎良.色氨酸/犬尿氨酸代谢途径与心血管疾病[J].中华高血压杂志,2012,20(5):433-435.
[13]Halford JC,Harrold JA,Boyland EJ,et al.Serotonergic drugs:effects on appetite suppression and use for the treatment of obesity[J].Drugs,2007,67(1):27-55.
[14]段云峰,吴晓丽,王涛,等.五羟色胺和多巴胺与攻击行为的关联研究进展[J].生命科学,2013,25(10):1027-1035.
[15]孙红暖,杨海明,王志跃,等.精氨酸对动物的营养生理及免疫作用[J].动物营养学报,2014,26(1):54-62.