中药复方颗粒对D-半乳糖致衰老模型小鼠尿液的核磁共振氢谱代谢组学研究

Hydrogen-nuclear magnetic resonance metabolomics study on the urine of D-galactose-induced aging model mice by Chinese compound granules

目的采用基于核磁共振氢谱(hydrogen-nuclear magnetic resonance, ~1H-NMR)的代谢组学研究方法探讨一种中药复方颗粒对D-半乳糖致衰老模型小鼠尿液代谢的影响。方法昆明小鼠48只,雄性,随机分为正常对照组、衰老模型组、阳性对照组、中药复方颗粒低、中、高剂量给药组;采用D-半乳糖致小鼠衰老模型,用中药复方颗粒进行药物干预,各组小鼠末次给药后收集24h内的尿液进行~1H-NMR检测,随后采用偏最小二乘法-判别式分析(partialleastsquares-discriminantanalysis,PLS-DA)及正交偏最小二乘法-判别式分析(orthogonal partial least squares-discriminant analysis, OPLS-DA)的方法对6组小鼠尿液代谢物进行模式识别分析并构建相应的代谢通路。结果代谢组学分析发现小鼠尿液中有超低密度脂蛋白(very low-densitylipoprotein,VLDL)、异亮氨酸、亮氨酸、乳酸、丙氨酸、胆碱、蛋氨酸、丙酮酸、琥珀酸、α-酮戊二酸、柠檬酸、二甲胺、三甲胺、牛磺酸、甘氨酸、肌酸、尿囊素、尿素、马尿酸、甲酸等20个差异代谢物;以及缬氨酸、亮氨酸和异亮氨酸的生物合成,牛磺酸和亚牛磺酸代谢,乙醛酸和二羧酸代谢,甘氨酸、丝氨酸和苏氨酸代谢,柠檬酸循环(TCA循环),丙酮酸代谢,半胱氨酸和蛋氨酸代谢等7个相关代谢通路。结论 D-半乳糖诱导的衰老模型小鼠的能量代谢、氨基酸代谢和炎症反应相关通路紊乱,而中药复方颗粒对其紊乱有一定的改善作用。

Objective To investigate the effects of Chinese medicine compound granules on urine metabolism in D-galactose-induced aging mice by hydrogen-nuclear magnetic resonance(~1H-NMR)method based metabolomics.Methods Forty-eight Kunming mice(male)were randomly divided into normal control group,aging model group,positive control group,low,middle and high dose group of Chinese medicine compound granules.Mice aging model was induced by D-galactose,and drug intervention was carried out with compound granules of traditional Chinese medicine.After the final administration,urine within 24 h in each group was collected for^1H-NMR detection,and partial least squares-discriminant analysis(OPLS-DA)and orthogonal partial least squares-discriminant analysis(PLS-DA)methods were conducted to distinguish and analyze the metabolic phenotypes and establish metabolic pathway.Results Metabonomic analysis revealed that there were 20 different metabolites in mouse urine,including very low-density lipoprotein(VLDL),isoleucine,leucine,lactic acid,alanine,choline,methionine,pyruvic acid,succinic acid,α-ketoglutaric acid,citric acid,dimethylamine,trimethylamine,taurine,glycine,creatine,allantoin,urea,hippuric acid,and formic acid;and 7 metabolic pathways such as valine,leucine and isoleucine biosynthesis,taurine and hypotaurine metabolism,glyoxylate and dicarboxylate metabolism,glycine、serine and threonine metabolism,citrate cycle(TCA cycle),pyruvate metabolism,cysteine and methionine metabolism.Conclusion The energy metabolism,amino acid metabolism and inflammation related pathway of D-galactose induced senescence model mice were disturbed,and Chinese medicine compound granules has certain improvement to its disorder.