Ju Hyun Kyoung, Chung Ha Wook, Lee Hee-Seung, Lim Johan, Park Jeong Hill, Lim Sung Cil, Kim Joon Mee, Hong Soon-Sun, Kwon Sung Won
College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Bioanalysis. 2013 Jan;5(1):41-51. doi: 10.4155/bio.12.296.
A metabolomic study of biomarkers associated with dimethylnitrosamine (DMN)-induced hepatic fibrosis in Sprague-Dawley rats was performed using GC-MS. The clinical chemistry of the collected blood and the histopathology of excised liver samples were examined, and urine samples were prepared by solvent extraction.
Through pattern analysis, the DMN-treated group was divided into two subgroups based on the aspartate aminotransferase (AST) levels compared with the control, a moderately higher group (DMN subgroup A) and a significantly higher group (DMN subgroup B). Uric acid, orotic acid, N-phenylacetylglycine and glutaric acid were biomarkers for DMN subgroup A, aminomalonic acid was a biomarker for DMN subgroup B, and arabitol level distinguished control versus DMN treatment regardless of AST level.
This study suggests that the identification and profiling of AST level-related metabolites may be useful as a diagnostic tool and for the study of the mechanism of liver fibrosis induced by DMN.
利用气相色谱 - 质谱联用仪（GC-MS）对与二甲基亚硝胺（DMN）诱导的斯普拉格 - 道利大鼠肝纤维化相关的生物标志物进行了代谢组学研究。检测了所采集血液的临床化学指标以及切除肝脏样本的组织病理学情况，并通过溶剂萃取制备了尿液样本。
通过模式分析，与对照组相比，根据天冬氨酸转氨酶（AST）水平，DMN处理组被分为两个亚组，一个是中度较高组（DMN亚组A）和一个显著较高组（DMN亚组B）。尿酸、乳清酸、N - 苯乙酰甘氨酸和戊二酸是DMN亚组A的生物标志物，氨基丙二酸是DMN亚组B的生物标志物，无论AST水平如何，木糖醇水平都能区分对照组和DMN处理组。
本研究表明，与AST水平相关的代谢物的鉴定和分析可能作为一种诊断工具以及用于研究DMN诱导肝纤维化的机制。
