基于尿液代谢组学技术研究尿毒清颗粒治疗慢性肾功能衰竭的机制

目的: 运用代谢组学方法研究尿毒清对慢性肾功能衰竭（CRF）大鼠尿液代谢谱的影响，并探讨其机制。方法: 36只大鼠随机分为空白对照组、模型对照组和尿毒清组。采用腺嘌呤法制备大鼠CRF模型。运用超高效液相色谱串联四极杆飞行时间质谱技术结合主成分分析和偏最小二乘判别分析，比较空白对照组、模型对照组、尿毒清组大鼠尿液的代谢谱，筛选出变量重要性投影值>1且P < 0.05的内源性物质作为CRF潜在的生物学标志物，并进行代谢通路的富集分析。结果: 与空白对照组比较，模型对照组大鼠体质量降低、肾脏系数增高、血清肌酐和尿素氮水平升高（均P < 0.01），而尿毒清组上述指标较模型对照组均有所改善（均P < 0.01）。共鉴定出15个潜在生物学标志物，涉及9条代谢通路紊乱，分别为苯丙氨酸、酪氨酸、色氨酸的生物合成，乙醛酸和二羧酸代谢，缬氨酸、亮氨酸、异亮氨酸生物合成，花生四烯酸代谢，半胱氨酸和蛋氨酸代谢，三羧酸循环，甘油磷脂代谢，色氨酸代谢，酪氨酸代谢。结论: 尿毒清对CRF大鼠具有一定的治疗作用，其机制可能与调节氨基酸代谢、脂质代谢和能量代谢等有关。

Effects of Niaoduqing granule on urine metabolic profile in chronic renal failure rats

Objective: To investigate the effects of Niaoduqing granule on the urine metabolic profile in chronic renal failure (CRF) rats. Methods: Thirty six male SD rats were divided into the normal control group, the model group, and the Niaoduqing group with 12 rats in each group. The CRF was induced by gavage of 250 mg·kg^-1·d^-1 adenine for 21 d. UPLC-Q-TOF-MS/MS technique was used in combination with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to analyze the urine metabolic profiles in three groups. The endogenous substances with the variable importance projection (VIP)>1 and P < 0.05 were screened as the potential biomarkers for CRF, and enrichment analysis of metabolic pathways was carried out. Results: Compared with the normal control group, the model group had lower body weight, higher kidney coefficient, higher serum creatinine and urea nitrogen levels (all P < 0.01), while the above indexes in the Niaoduqing group were ameliorated compared with the model group (all P < 0.01). Fifteen potential biomarkers were found in the urine of the model group, which were involved in 9 metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, glyoxylate and dicarboxylate metabolism, valine, leucine and isoleucine biosynthesis, arachidonic acid metabolism, cysteine and methionine metabolism, tricarboxylic acid cycle, glycerophosphatide metabolism, tryptophan metabolism and tyrosine metabolism. Conclusion: Niaoduqing granules has therapeutic effect on rats with CRF, which may be related to the regulation of amino acid metabolism, lipid metabolism and energy metabolism.