雷公藤甘草配伍干预肾病综合征大鼠的血清代谢组学分析

Serum Metabonomics Analysis of Leigongteng(Tripterygium wilfordii)Combined with Gancao(Glycyrrhiza)on Rats with Nephrotic Syndrome

目的采用代谢组学方法研究雷公藤甘草配伍后,肾病综合征大鼠血清内源性物质的动态变化,提示配伍减毒增效机制。方法取SD大鼠,进行随机分组:空白组、模型组、雷公藤给药组(TPW组)和雷公藤甘草配伍给药组(TPW-GLY组)。应用UPLC-Q-TOF-/MS技术手段,识别血清样品的代谢物谱,并采用PCA和OPLS-DA进行生物标记物鉴定。结果4组大鼠血清的代谢轮廓具有显著差异,空白组与模型组间识别出24个具有显著性差异的生物标记物,有21个生物标记物在TPW-GLY组内识别并回调,有15个生物标记物在TPW组中被回调。最终筛选并鉴定了7个内源性生物标记物,分别为溶血磷脂酰胆碱(22:6[4Z,7Z,10Z,13Z,16Z,19Z])、磷脂酰乙醇胺(24:1[15Z]/15:0)、油酸酰胺、花生四烯酸、亚油酸、棕榈酸、油酸。结论通过雷公藤甘草配伍后,血清中7种生物标记物水平发生变化,可能改善了肾病综合征大鼠机体的磷脂代谢、脂肪酸生物合成与代谢、花生四烯酸新陈代谢等过程,起到减毒增效的作用。

Objective Metabolomics method was used to study the dynamic changes of serum endogenous substances in rats with nephrotic syndrome after the compatibility of Leigongteng(Tripterygium wilfordii)combined with Gancao(Glycyrrhiza).Methods SD rats were randomly divided into blank group,model group,Leigongteng(Tripterygium wilfordii)administration group(TPW group)and Leigongteng(Tripterygium wilfordii)combined with Gancao(Glycyrrhiza)group(TPW-GLY group).UPLC-Q-TOF-/MS was used to identify metabolite profiles of serum samples,and principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were used to identify biomarkers.Results There were significant differences in serum metabolic profiles of the four groups,24 biomarkers with significant differences were identified between the blank group and the model group,21 biomarkers were identified and called back in the TPW-Gly group,and 15 biomarkers were called back in the TPW group.Seven endogenous biomarkers were screened and identified,which were ysophosphatidylcholine(22:6[4 Z,7 Z,10 Z,13 Z,16 Z,19 Z]),phosphatidylethanolamine(24:1[15 Z]/15:0),oleic amide,arachidonic acid,linoleic acid,palmitic acid and oleic acid.Conclusion Through the combination of Leigongteng(Tripterygium wilfordii)and Gancao(Glycyrrhiza),the levels of 7 biomarker in serum changed,which may improve the phospholipid metabolism,fatty acid biosynthesis and metabolism,arachidonic acid metabolism and other processes in rats with nephrotic syndrome,and play a role of reducing toxicity and increasing efficiency.