大鼠肝再生氨基酸靶向代谢组学分析

Targeted metabolomics analysis of amino acid during rat liver regeneration

目的探讨氨基酸代谢对大鼠肝再生(LR)的调控作用。方法大鼠随机分为10组,每组5只,包括9个部分肝切除组(PH)和1个正常对照组。运用质谱选择反应检测扫描/多反应检测扫描(SRM/MRM)对大鼠肝再生中10个时间点的20种氨基酸的含量进行靶向代谢组学鉴定,并对氨基酸含量变化进行聚类分析。结果丙氨酸在30、36和72 h上调;精氨酸在6和12 h上调;天冬氨酸在6、12和36 h上调;谷氨酸在6、12、30、36、72和120 h上调;组氨酸在12、24、30、36、72和120 h上调;谷氨酰胺在72 h上调;异亮氨酸在24 h下调。通过对氨基酸聚类分析发现,这些氨基酸可以聚为3类。结论肝再生过程中多种氨基酸发生了变化,且贯穿大鼠肝再生的全过程。氨基酸含量的变化,对肝再生中肝细胞增殖有重要作用。

Objective To explore the regulation of amino acid metabolism during rat liver regeneration(LR).Methods Rats were randomly divided into 10 groups with 5 rats in each group,including nine partial hepatectomy(PH)groups and one normal control group.Selective reaction monitoring/multi reaction monitoring(SRM/MRM)was employed in the targeted metabolomics identification of 20 amino acids at 10 time points in rat liver regeneration.The change of amino acid content was analyzed by hierarchical clustering.Results Alanine was up-regulated at 30,36 and 72 hours;arginine was up-regulated at 6 and 12 hours;aspartic acid was up-regulated at 6,12 and 36 hours;glutamate was up-regulated at 6,12,30,36,72 and 120 hours;histidine was up-regulated at 12,24,30,36,72 and 120 hours;glutamine was upregulated at 72 hours,and isoleucine was down-regulated at 24 hours.Through hierarchical clustering analysis of amino acids,these amino acids can be grouped into three clusters.Conclusion Many amino acids have changed during the liver regeneration,and throughout the whole process of rat liver regeneration.Changes in amino acids content play an important role in hepatocyte proliferation during the liver regeneration.