山东医药2016，Vol.56Issue(46)：1-6,6.DOI:10.3969/j.issn.1002-266X.2016.46.001
顺铂肾损害大鼠三七总皂苷干预前后尿液的核磁共振代谢组学分析
Nuclear magnetic resonance metabonomics analysis of urine from rat with cisplatin-incuced nephrotoxicity before and after Panax notoginseng saponins intervention
摘要
Abstract
Objective To metabonomically analyze the urine samples from rats with cisplatin-induced nephrotoxicity before and after Panax notoginseng saponins (PNS)treatment by 1 H nuclear magnetic resonance-based metabonomics (1 H NMR),in order to provide basis for the study of PNS protecting cisplatin-induced renal injury.Methods Forty-five male SD rats were randomly divided into the normal control group,the cisplatin-only group and the cisplatin-PNS group (n=15, in each group).Rats in the cisplatin-only group and the cisplatin-PNS group were exposed to a single dose of cisplatin 5 mg/kg to induce renal damage.Rats in the cisplatin-PNS group were injected with 31.35 mg/kg PNS from day 1 to day 8. After exposure to cisplatin for 1 ,4 and 8 days,the urine samples were analyzed using 1 H NMR combined with multivariate pattern recognition.After centrifugation,500 μL of the supernatant was placed in a nuclear magnetic tube,and urine was detected using a Varian 600 magnetic spectrometer to obtain an NMR spectrum.The normalized NMR data were analyzed by SIMCA-P+software for pattern recognition.The principal component analysis (PCA)was carried out with centralization conversion.Partial least-squares discriminant analysis (PLS-DA)was carried out by using the adaptive conversion.Orthog-onal partial least squares-discriminant analysis (OPLS-DA ) was applied to orthogonally correct PLS-DA model.We screened the statistically significant metabolites through the analysis of OPLS-DA and by analyzing the corresponding corre-lation coefficient of each metabolite.The metabolic pathways of different metabolites were obtained by mapping ID in the KEGG database of different metabolites.Results The urine 1 H NMR spectra from the normal control group,the cisplatin-only group and the cisplatin-PNS group contained many metabolites,including acetoacetate,acetone,citrate,formate and glucose.Additionally,the Multivariate analysis in PCA,PLS-DA and OPLS-DA showed that there was a significant differ-ence between the normal control group and cisplatin-only group,cisplatin-PNS group,and there was a part overlap between the cisplatin-PNS group and the cisplatin-only group on day 1,4 and 8.Moreover on day 8,the expression ofβ-glu-cose,α-glucose,maltose and ethanolamine was lower,while the expression of pyruvate,succinate andα-ketoglutarate was higher in the cisplatin-only group.However,the expression ofβ-glucose,α-glucose,maltose and ethanolamine was high-er,while the expression of pyruvate,succinate and α-ketoglutarate was lower in the cisplatin-PNS group as compared with that of the cisplatin-only group,and PNS could significantly callback the metabolites with abnormal expression.The altera-tions of metabolic pathways mainly included biosynthesis of amino acids,citrate cycle,glycolysis/gluconeogenesis,pentose phosphate pathway,glycerol phospholipid metabolism,pyruvate metabolism,synthesis and degradation of ketone bodies and phenylalanine metabolism.Conclusion The metabolites in urine change after exposure to cisplatin in rats.PNS could improve some metabolites,such as energy metabolism,glucose metabolism,amino acid metabolism and fat metabolism, these may be important mechanisms in PNS protecting against cisplatin-induced renal injury.关键词
三七总皂苷/顺铂/肾损害/核磁共振/差异代谢物/尿液/代谢组学Key words
Panax notoginseng saponins/Cisplatin/renal injury/nuclear magnetic resonance/differences metabo-lites/urine/metabonomics分类
医药卫生引用本文复制引用
黄振光,杨玉芳,邹小琴,黄春,周金玲..顺铂肾损害大鼠三七总皂苷干预前后尿液的核磁共振代谢组学分析[J].山东医药,2016,56(46):1-6,6.基金项目
国家自然科学基金资助项目（81260598，81560729）。 （）
