Biomedical Research Laboratories, Kureha Corporation, Tokyo, Japan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jun 15;878(20):1662-8. doi: 10.1016/j.jchromb.2009.11.040. Epub 2009 Dec 3.
We applied the metabolomic analysis of comprehensive small-molecular metabolites using liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) and principal component analysis to identify uremic toxins accumulated in the serum of chronic renal failure (CRF) rats. CRF rats were produced by 5/6-nephrectomy. Indoxyl sulfate was demonstrated to be the first principal serum metabolite which differentiates CRF from normal, followed by phenyl sulfate, hippuric acid and p-cresyl sulfate. Then, we measured the serum levels of indoxyl sulfate, phenyl sulfate, hippuric acid and p-cresyl sulfate by the selected reaction monitoring (SRM) of LC/ESI-MS/MS, and demonstrated that these serum levels were markedly increased in CRF rats as compared with normal rats. As creatinine clearance decreased, the serum levels of the metabolites increased.
我们采用液相色谱/电喷雾串联质谱（LC/ESI-MS/MS）和主成分分析对慢性肾衰竭（CRF）大鼠血清中蓄积的尿毒症毒素进行全面小分子代谢物的代谢组学分析。CRF 大鼠通过 5/6 肾切除术产生。硫酸吲哚酚被证明是第一个将 CRF 与正常大鼠区分开来的主要血清代谢物，其次是硫酸对甲酚、马尿酸和对羟甲苯磺酸。然后，我们通过液相色谱/电喷雾串联质谱的选择反应监测（SRM）测量了血清中硫酸吲哚酚、硫酸对甲酚、马尿酸和对羟甲苯磺酸的水平，并证实这些代谢物的水平在 CRF 大鼠中明显高于正常大鼠。随着肌酐清除率的降低，这些代谢物的血清水平也随之升高。
