大鼠肝再生氨基酸靶向代谢组学分析

杨晖; 徐存拴

doi:10.16098/j.issn.0529-1356.2021.02.008

PDF(2481 KB)

解剖学报 ›› 2021, Vol. 52 ›› Issue (2) : 210-215. DOI: 10.16098/j.issn.0529-1356.2021.02.008

细胞和分子生物学

大鼠肝再生氨基酸靶向代谢组学分析

杨晖^1,2 徐存拴^1,2*

作者信息 +

Targeted metabolomics analysis of amino acid during rat liver regeneration

YANG Hui^{1, 2} XU Cun-shuan^{1, 2*}

Author information +

文章历史 +

摘要

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。

Abstract

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 up-regulated 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.

导出引用

杨晖徐存拴. 大鼠肝再生氨基酸靶向代谢组学分析[J]. 解剖学报. 2021, 52(2): 210-215 https://doi.org/10.16098/j.issn.0529-1356.2021.02.008

YANG Hui XU Cun-shuan. Targeted metabolomics analysis of amino acid during rat liver regeneration[J]. Acta Anatomica Sinica. 2021, 52(2): 210-215 https://doi.org/10.16098/j.issn.0529-1356.2021.02.008

中图分类号： R575

参考文献

［1］ Zang XY, Geng XF, Zhang ChY, et al. Role of microRNAs in liver regeneration ［J］. Acta Anatomica Sinica, 2017, 48 (2): 230-235. (in Chinese)

臧夏炎, 耿小芳, 张春艳, 等. MicroRNAs在肝再生中的作用研究进展［J］. 解剖学报, 2017, 48 (2): 230-235.

［2］ Xing XK, Li MH, Xu CSh. Expression changes of AKT,ATM,D4-GDI and p53 cell apoptosis pathway genes in the process of rat liver regeneration ［J］. Acta Anatomica Sinica, 2016, 47 (3): 315-322. (in Chinese)

邢雪琨, 李梦华, 徐存拴. AKT、ATM、D4-GDI和p53 4条细胞凋亡通路基因在大鼠肝再生过程中的表达变化［J］. 解剖学报, 2016, 47 (3): 315-322.

［3］ Chou KC. Prediction of tight turns and their types in proteins ［J］. Anal Biochem, 2000, 286(1):1-16.

［4］ Chou KC. Modelling extracellular domains of GABA-A receptors: subtypes 1, 2, 3, and 5 ［J］. Biochem Biophys Res Commun, 2004, 316(3): 636-642.

［5］ Chou KC, Shen HB. Signal-CF: a subsite-coupled and window-fusing approach for predicting signal peptides ［J］. Biochem Biophys Rese Commun, 2007, 357(3): 633-640.

［6］ Xu C, Chen X, Chang C, et al. Transcriptome analysis of hepatocytes after partial hepatectomy in rats ［J］. Deve Genes Evol, 2010, 220(9-10): 263-274.

［7］ Sonntag D, Scandurra FM, Friedrich T, et al. Targeted metabolomics for bioprocessing［J］. BMC Proc, 2011, 5(Suppl 8): 27.

［8］ Ito K, Ozasa H, Noda Y, et al. Effect of non-essential amino acid glycine administration on the liver regeneration of partially hepatectomized rats with hepatic ischemia/reperfusion injury［J］. Clin Nutr, 2008, 27(5): 773-780.

［9］ Yuan Y, Wu X, Ou Q, et al. Differential expression of the genes involved in amino acids and nitrogen metabolisms during liver regeneration of mice ［J］. Hepatology Res, 2009, 39(3): 301-312.

［10］ Chiba T, Kawai K, Ikenaka K, et al. Effect of an exogenous energy source and amino acids on DNA synthesis in regenerating rat liver ［J］. Biochim Biophysica Acta, 1983, 755(3): 420-427.

［11］ Mead JE, Braun L, Martin DA, et al. Induction of replicative competence (“priming”) in normal liver ［J］. Cancer Res, 1990, 50(21): 7023-7030.

［12］ Nelsen CJ, Rickheim DG, Tucker MM, et al. Amino acids regulate hepatocyte proliferation through modulation of cyclin D1 expression ［J］. J Biol Chem, 2003, 278(28): 25853-25858.

［13］ Holecek M, Vodenicarovova M. Phenylbutyrate exerts adverse effects on liver regeneration and amino acid concentrations in partially hepatectomized rats ［J］. Int J Exp Pathol, 2016, 97(3): 278-284.

［14］ Yin L, Chang C, Xu C. Expressions profiles of the proteins associated with carbohydrate metabolism in rat liver regeneration ［J］. Biomed Rese Int, 2017, 2017(7): 8428926.

［15］ Tanaka T, Ando M, Yamashita T, et al. Effects of alanine and glutamine administration on the inhibition of liver regeneration by acute ethanol treatment ［J］. Alcohol Alcohol Suppl, 1993, 1B: 41-45.

［16］ Yoshida S, Yunoki T, Aoyagi K, et al. Effect of glutamine supplement and hepatectomy on DNA and protein synthesis in the remnant liver ［J］. J Surg Res, 1995, 59(4): 475-481.

［17］ Schmitt B, Vicenzi M, Garrel C, et al. Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: a comparative crossover study ［J］. Redox Biol, 2015, 6(12):198-205.

［18］ Kurokawa T, An J, Tsunekawa K, et al. Effect of L-arginine supplement on liver regeneration after partial hepatectomy in rats ［J］. World J Surg Oncology, 2012, 10:99.

［19］ Chang CF, Fan JY, Zhang FC, et al. Transcriptome atlas of eight liver cell types uncovers effects of histidine catabolites on rat liver regeneration ［J］. J Genet, 2010, 89(4): 425-436.

［20］ Patel D, Menon D, Bernfeld E, et al. Aspartate rescues S-phase arrest caused by suppression of glutamine utilization in KRas-driven cancer cells ［J］. J Biol Chem, 2016, 291(17): 9322-9329.

［21］ Spolter PD, Harper AE. Effect of leucine-isoleucine and valine antagonism and comparison with the effect of ethionine on rat liver regeneration ［J］. Arch Biochem Biophys, 1963, 100(3):369-377.