基于代谢组学分析儿童紫癜性肾炎证候学标记物研究

Metabonomics Analysis of Syndrome Markers in Children Henoch-Schonlein Purpura Nephritis

目的:运用超高液相色谱与质谱联用技术(UPLC-MS/MS)分析儿童紫癜性肾炎热伤肾络证尿液代谢物,开展中医证候学标记物研究。方法:收集紫癜性肾炎患儿热伤肾络证、非热伤肾络证及健康儿童的尿液,利用UPLC-MS/MS检测分析其代谢指纹谱,用主成分分析(PCA)、正交偏最小二乘法(OPLS-DA)判别分析图谱,通过变量重要性投影值(VIP)和非参数检验分析筛选,确定组间差异性代谢物。结果:与健康对照组比较,紫癜性肾炎患儿尿中雌酮、色氨酰蛋氨酸、苯丙精氨酸、磷脂酰胆碱、胆甾-3,7,12,25四醇-3-葡糖苷酸、乙酰乙酸、N2,N2-二甲基鸟苷含量降低(P<0.05),精氨酰丝氨酸、同型半胱氨酸硫内酯含量升高(P<0.05);热伤肾络证患儿尿中苯丙精氨酸、L-蛋氨酸、雌酮、色氨酰蛋氨酸含量下降(P<0.05);醛固酮、均聚L-精氨酸、同型半胱氨酸硫内酯含量升高(P<0.05)。结论:儿童紫癜性肾炎与健康小儿尿液代谢物具有差异性,儿童紫癜性肾炎不同证型间存在代谢标记物基础。

Objective： To analyze the urinary metabolite in children with henoch schonlein purpura nephritis（HSPN） in thermal injury kidney collaterals syndrome by using ultra high liquid chromatograph and mass spectrometry（UPLC-MS/MS）, so as to conduct the research on TCM syndrome markers. Methods： Collected urine of children in thermal injury kidney collaterals syndrome of HSPN and non-thermal injury kidney collaterals syndromed as well as those of healthy children to conduct UPLC-MS/MS. Using the principal component analysis（PCA） and orthogonal partial least squares（OPLS-DA）, we analyzed the profiles and variable importance projection value（VIP） and non-parametric test analysis to filter. The different metabolites were determined. Results：Contents of substances like estrone, tryptophyl-methionine, phenylalanyl-arginine, phosphatidylcholine, cholestane-3,7,12,25-tetrol-3-glucuronide, acetoacetic acid, N2,N2-dimethylguanosine in HSPN children＇s urine declined（P〈0.05）, while arginyl-serine, homocysteine thiolactone increased, as compared with those of health（P〈0.05）. Contents of phenylalanyl-arginine, L-methionine, estrone, tryptophyl-methionine in thermal injury kidney collaterals syndrome of HSPN group declined, and aldosterone, homo-L-arginine, homocysteine thiolactone increased, as compared with healthy children（P〈0.05）. Conclusion： Urine metabolites in HSPN and health children are different, and there is basis of metabolic markers in different syndromes of HSPN.