摘要
采用气相-质谱联用技术测定空白组和D-氨基半乳糖组大鼠血清中15种脂肪酸的含量,结合主成分分析和偏最小二乘法-判别分析等化学计量学方法分析大鼠腹腔注射D-氨基半乳糖后脂肪酸代谢轮廓的变化和生物标识物。结果表明,D-氨基半乳糖组大鼠血清中4种游离脂肪酸和10种酯化脂肪酸的含量显著降低,且脂肪酸代谢轮廓明显偏离正常水平;硬脂酸、花生四烯酸和顺式-4,7,10,13,16,19-二十二碳六烯酸(DHA)对表征D-氨基半乳糖肝毒性具有重要贡献,且与丙氨酸氨基转移酶、天门冬氨酸氨基转移酶和碱性磷酸酶呈良好的负相关性,被鉴定为D-氨基半乳糖肝毒性的潜在生物标识物。本研究为化学肝损伤的评价和毒性机制研究提供新的思路和方法。
The serum concentration of 15 fatty acids were determined in vehicle-and D-galactosamine（D-Gal N）-treated rats using a gas chromatography-mass spectrometry method, and subsequent analysis of fatty acid metabolic profiling and biomarkers by principal component analysis and partial least squares-discriminant analysis. The results indicated that serum levels of 4 free fatty acids and 10 esterified fatty acids in D-Gal N-treated rats decreased significantly when compared to vehicle-treated rats, and the metabolic profiling of fatty acids in D-Gal N group noticeably deviated from normal level.More importantly, stearic acid, arachidonic acid and docosahexaenoic acid（DHA） were important indicators of liver injury induced by D-Gal N, the concentrations of which were all negatively correlated with the levels of alanine aminotransferase,aspartate aminotransferase and alkaline phosphatase. Therefore, the three fatty acids were identified as potential biomarkers of hepatotoxicity induced by D-Gal N. The project provides a new idea and method for the evaluation and toxicity mechanism research of chemical liver injury.
作者
刘晓杰
黎红维
熊印华
Liu Xiaojie;Li Hongwei;Xiong Yinhua(School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, China;Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, Nanchang 330013, China)
出处
《江西科技师范大学学报》
2017年第6期71-76,共6页
Journal of Jiangxi Science & Technology Normal University
基金
国家自然科学基金项目(81660692)
江西省教育厅科学技术研究项目(GJJ14598)
江西科技师范大学研究生创新专项基金项目(YC2016-X17)
江西省药物分子设计与评价重点实验室(20171BCD40015)
关键词
D-氨基半乳糖
脂肪酸
肝损伤
代谢轮廓
D-galactosamine
fatty acids
liver injury
metabolic profiling
