药学学报, 2018, 53(7): 1122-1130
引用本文:
张佳璇, 孙琅, 庞晶, 胡辛欣, 聂彤颖, 卢曦, 王秀坤, 杨信怡, 游雪甫, 李聪然. 肺炎克雷伯杆菌感染小鼠脓毒症模型的非靶向代谢组学研究[J]. 药学学报, 2018, 53(7): 1122-1130.
ZHANG Jia-xuan, SUN Lang, PANG Jing, HU Xin-xin, NIE Tong-ying, LU Xi, WANG Xiu-kun, YANG Xin-yi, YOU Xue-fu, LI Cong-ran. Non-targeted metabolomics in septic mice infected with Klebsiella pneumoniae[J]. Acta Pharmaceutica Sinica, 2018, 53(7): 1122-1130.

肺炎克雷伯杆菌感染小鼠脓毒症模型的非靶向代谢组学研究
张佳璇, 孙琅, 庞晶, 胡辛欣, 聂彤颖, 卢曦, 王秀坤, 杨信怡, 游雪甫, 李聪然
中国医学科学院医药生物技术研究所, 抗感染药物研究北京市重点实验室, 北京 100050
摘要:
脓毒症是医学界面临的突出难题,本研究采用超高效液相色谱与串联四级杆飞行质谱(UHPLC-QTOF-MS)联用技术对肺炎克雷伯杆菌ATCC® BAA 2146感染小鼠脓毒症模型进行了非靶向代谢组学研究,分析小鼠感染后血浆内源性代谢物的变化,筛选出与脓毒症感染相关的潜在生物标志物,并分析相关的代谢通路。结果表明,经主成分分析和偏最小二乘法判别分析,结合变量投影重要度与非参数检验共筛选鉴定出58种可能与肺炎克雷伯杆菌ATCC® BAA 2146感染小鼠脓毒症相关的代谢物。相关的代谢通路分析发现其中18种代谢物与烟酸和烟酰胺代谢、嘧啶代谢、维生素B6代谢、牛磺酸和亚牛磺酸代谢、精氨酸和脯氨酸代谢、丙氨酸、天冬氨酸和谷氨酸代谢、D-谷氨酰胺和D-谷氨酸代谢以及甘油磷脂代谢等8个代谢通路密切相关。
关键词:   
Non-targeted metabolomics in septic mice infected with Klebsiella pneumoniae
ZHANG Jia-xuan, SUN Lang, PANG Jing, HU Xin-xin, NIE Tong-ying, LU Xi, WANG Xiu-kun, YANG Xin-yi, YOU Xue-fu, LI Cong-ran
Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
Abstract:
UHPLC-QTOF-MS was applied to non-targeted metabolomics study of mice infected with K. pneumoniae ATCC® BAA 2146 to discover potential biomarkers and metabolic pathways that are associated with sepsis. Fifty-eight metabolites were identified by principal components analysis (PCA) and partial least-squares discriminant analysis (OPLS-DA), which was combined with variable projection importance (VIP) and nonparametric test. Eighteen of the 58 metabolites were further found to be involved in 8 metabolic pathways, including nicotinate and nicotinamide metabolism, pyrimidine metabolism, vitamin B6 metabolism, taurine and hypotaurine metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism and glycerophospholipid metabolism.
Key words:   
收稿日期: 2018-02-08
DOI: 10.16438/j.0513-4870.2018-0145
基金项目: 国家高技术研究发展计划(863计划)资助项目(2014AA021101);中国医学科学院医学与健康科技创新工程(2016-I2M-3-014);“十三五”国家科技重大专项(2018ZX09721001);国家自然科学基金资助项目(81361138020).
通讯作者: 游雪甫,Tel:86-10-67061033,E-mail:xuefuyou@hotmail.com;李聪然,Tel:86-10-67058991,E-mail:cong5885@aliyun.com
Email: xuefuyou@hotmail.com;cong5885@aliyun.com
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