新生儿败血症的代谢组学改变：一项探索性临床研究

doi:10.7499/j.issn.1008-8830.2112020

摘要
图/表
参考文献(33)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (760 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的通过分析新生儿败血症患儿入院后不同时间的血清显著性差异代谢物主要涉及的代谢通路，以探索该病在不同阶段的代谢机制。方法选择2019年1月1日至2020年1月1日在湖南省人民医院新生儿科住院的新生儿败血症患儿为败血症组（n=20），采集入院第1天、第4天、第7天的静脉血标本；选择同期健康新生儿为健康对照组（n=10）。采用超高效液相色谱-四级杆飞行时间串联质谱技术对血清标本进行代谢组学分析，探讨不同时间败血症患儿代谢组学变化。结果败血症组入院第1天时与健康对照组相比，血清差异代谢物主要涉及萜类骨架的生物合成；败血症组入院第4天时与入院第1天时相比，血清差异代谢物主要涉及丙酮酸代谢；败血症组入院第7天时与入院第4天时相比，血清差异代谢物主要涉及半胱氨酸和蛋氨酸代谢；败血症组入院第7天时与入院第1天时相比，血清差异代谢物主要涉及抗坏血酸代谢。结论不同阶段新生儿败血症患儿血清代谢物的代谢机制不同，主要与萜类骨架生物合成、丙酮酸代谢、半胱氨酸和蛋氨酸代谢、抗坏血酸代谢途径相关。引

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	童平
	黄芙蓉
	徐俊
	伍紫琦
	胡杏
	凌鸣
	王蝶
	吴不非
	杨独娇
	张爱民

关键词 ：新生儿败血症, 代谢组学, 新生儿

Abstract：Objective To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission. Methods A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points. Results On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism. Conclusions The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.

Key words： Neonatal sepsis Metabolomics Neonate

收稿日期: 2021-12-04

基金资助:湖南省教育厅科学研究项目（20C1148）。

通讯作者: 张爱民，女，主任医师。Email：lilly610@sina.com。 E-mail: lilly610@sina.com

作者简介: 童平，女，硕士，住院医；

引用本文:

童平,黄芙蓉,徐俊等. 新生儿败血症的代谢组学改变：一项探索性临床研究[J]. 中国当代儿科杂志, 2022, 24(6): 675-680.

TONG Ping,HUANG Fu-Rong,XU Jun et al. Metabolomic changes of neonatal sepsis: an exploratory clinical study[J]. CJCP, 2022, 24(6): 675-680.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2112020 或 http://www.zgddek.com/CN/Y2022/V24/I6/675

	中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会. 新生儿败血症诊断及治疗专家共识(2019年版)[J]. 中华儿科杂志, 2019, 57(4): 252-257. PMID: 30934196. DOI: 10.3760/cma.j.issn.0578-1310.2019.04.005.
	2 WrightS, Mathieson K, Brearley L, et al. Ending newborn deaths—ensuring every baby survives[M]. London: Save the Children, 2014: 1-46.
	Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, et al. The global burden of paediatric and neonatal sepsis: a systematic review[J]. Lancet Respir Med, 2018, 6(3): 223-230. PMID: 29508706. DOI: 10.1016/S2213-2600(18)30063-8.
	4 王卫平, 孙锟, 常立文, 等. 儿科学[M]. 9版. 北京: 人民卫生出版社, 2018: 122-124.
	Oza S, Lawn JE, Hogan DR, et al. Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000-2013[J]. Bull World Health Organ, 2015, 93(1): 19-28. PMID: 25558104. PMCID: PMC4271684. DOI: 10.2471/BLT.14.139790.
	Lin ZY, Xu PB, Yan SK, et al. A metabonomic approach to early prognostic evaluation of experimental sepsis by 1H NMR and pattern recognition[J]. NMR Biomed, 2009, 22(6): 601-608. PMID: 19322815. DOI: 10.1002/nbm.1373.
	Shane AL, Stoll BJ. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis[J]. Am J Perinatol, 2013, 30(2): 131-141. PMID: 23297182. DOI: 10.1055/s-0032-1333413.
	Touil HFZ, Boucherit K, Boucherit-Otmani Z, et al. Optimum inhibition of amphotericin-B-resistant Candida albicans strain in single- and mixed-species biofilms by Candida and non-Candida terpenoids[J]. Biomolecules, 2020, 10(2): 342. PMID: 32098224. PMCID: PMC7072433. DOI: 10.3390/biom10020342.
	Cao L, Zhang X, Cao F, et al. Inhibiting inducible miR-223 further reduces viable cells in human cancer cell lines MCF-7 and PC3 treated by celastrol[J]. BMC Cancer, 2015, 15(1): 873. PMID: 26552919. PMCID: PMC4640397. DOI: 10.1186/s12885-015-1909-2.
	Gallily R, Yekhtin Z, Hanu? LO. The anti-inflammatory properties of terpenoids from Cannabis[J]. Cannabis Cannabinoid Res, 2018, 3(1): 282-290. PMID: 30596146. PMCID: PMC6308289. DOI: 10.1089/can.2018.0014.
	Liu H, Zhang Y, Sun S, et al. Efficacy of terpenoid in attenuating aortic atherosclerosis in apolipoprotein-E deficient mice: a meta-analysis of animal studies[J]. Biomed Res Int, 2019, 2019: 2931831. PMID: 31392210. PMCID: PMC6662500. DOI: 10.1155/2019/2931831.
	Shi Z, Chen Y, Lu C, et al. Resolving neuroinflammation, the therapeutic potential of the anti-malaria drug family of artemisinin[J]. Pharmacol Res, 2018, 136: 172-180. PMID: 30196102. DOI: 10.1016/j.phrs.2018.09.002.
	Yan X, Fan Y, Wei W, et al. Production of bioactive ginsenoside compound K in metabolically engineered yeast[J]. Cell Res, 2014, 24(6): 770-773. PMID: 24603359. PMCID: PMC4042165. DOI: 10.1038/cr.2014.28.
	Wright CW. Traditional antimalarials and the development of novel antimalarial drugs[J]. J Ethnopharmacol, 2005, 100(1-2): 67-71. PMID: 16023812. DOI: 10.1016/j.jep.2005.05.012.
	Cuzzocrea S, Riley DP, Caputi AP, et al. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury[J]. Pharmacol Rev, 2001, 53(1): 135-159. PMID: 11171943.
	Salahudeen AK, Clark EC, Nath KA. Hydrogen peroxide-induced renal injury. A protective role for pyruvate in vitro and in vivo[J]. J Clin Invest, 1991, 88(6): 1886-1893. PMID: 1752950. PMCID: PMC295757. DOI: 10.1172/JCI115511.
	Kang H, Mao Z, Zhao Y, et al. Ethyl pyruvate protects against sepsis by regulating energy metabolism[J]. Ther Clin Risk Manag, 2016, 12: 287-294. PMID: 26966369. PMCID: PMC4770074. DOI: 10.2147/TCRM.S97989.
	邓子辉, 遆冬冬, 薛辉, 等. 丙酮酸乙酯对脓毒症小鼠器官损伤的影响[J]. 中国危重病急救医学, 2009, 21(8): 460-462. PMID: 19695165. DOI: 10.3760/cma.j.issn.1003-0603.2009.08.005.
	Yang R, Zhu S, Tonnessen TI. Ethyl pyruvate is a novel anti-inflammatory agent to treat multiple inflammatory organ injuries[J]. J Inflamm (Lond), 2016, 13: 37. PMID: 27980458. PMCID: PMC5135784. DOI: 10.1186/s12950-016-0144-1.
	Semmler A, Prost JC, Smulders Y, et al. Methylation metabolism in sepsis and systemic inflammatory response syndrome[J]. Scand J Clin Lab Invest, 2013, 73(5): 368-372. PMID: 23566119. DOI: 10.3109/00365513.2013.785587.
	Erdem SS, Yerlikaya FH, ?i?ekler H, et al. Association between ischemia-modified albumin, homocysteine, vitamin B12 and folic acid in patients with severe sepsis[J]. Clin Chem Lab Med, 2012, 50(8): 1417-1421. PMID: 22868807. DOI: 10.1515/cclm-2011-0794.
	Ploder M, Kurz K, Spittler A, et al. Early increase of plasma homocysteine in sepsis patients with poor outcome[J]. Mol Med, 2010, 16(11-12): 498-504. PMID: 20386870. PMCID: PMC2972395. DOI: 10.2119/molmed.2010.00008.
	Cambonie G, Bellet H, Houdon L, et al. Urinary excretion of free cysteine in critically ill neonates[J]. Acta Paediatr, 2001, 90(12): 1405-1410. PMID: 11853338. DOI: 10.1080/08035250152708815.
	Breuillé D, Béchereau F, Buffière C, et al. Beneficial effect of amino acid supplementation, especially cysteine, on body nitrogen economy in septic rats[J]. Clin Nutr, 2006, 25(4): 634-642. PMID: 16387396. DOI: 10.1016/j.clnu.2005.11.009.
	Garcia-Simon M, Morales JM, Modesto-Alapont V, et al. Prognosis biomarkers of severe sepsis and septic shock by 1H NMR urine metabolomics in the intensive care unit[J]. PLoS One, 2015, 10(11): e0140993. PMID: 26565633. PMCID: PMC4643898. DOI: 10.1371/journal.pone.0140993.
	Lin J, Falwell S, Greenhalgh D, et al. High-dose ascorbic acid for burn shock resuscitation may not improve outcomes[J]. J Burn Care Res, 2018, 39(5): 708-712. PMID: 29931212. DOI: 10.1093/jbcr/irx030.
	Carr AC, Rosengrave PC, Bayer S, et al. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes[J]. Crit Care, 2017, 21(1): 300. PMID: 29228951. PMCID: PMC5725835. DOI: 10.1186/s13054-017-1891-y.
	de Grooth HJ, Manubulu-Choo WP, Zandvliet AS, et al. Vitamin C pharmacokinetics in critically ill patients: a randomized trial of four IV regimens[J]. Chest, 2018, 153(6): 1368-1377. PMID: 29522710. DOI: 10.1016/j.chest.2018.02.025.
	Marik PE, Khangoora V, Rivera R, et al. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study[J]. Chest, 2017, 151(6): 1229-1238. PMID: 27940189. DOI: 10.1016/j.chest.2016.11.036.
	Wang Y, Lin H, Lin BW, et al. Effects of different ascorbic acid doses on the mortality of critically ill patients: a meta-analysis[J]. Ann Intensive Care, 2019, 9(1): 58. PMID: 31111241. PMCID: PMC6527630. DOI: 10.1186/s13613-019-0532-9.
	Tanaka H, Matsuda T, Miyagantani Y, et al. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study[J]. Arch Surg, 2000, 135(3): 326-331. PMID: 10722036. DOI: 10.1001/archsurg.135.3.326.
	Matsuda T, Tanaka H, Reyes HM, et al. Antioxidant therapy using high dose vitamin C: reduction of postburn resuscitation fluid volume requirements[J]. World J Surg, 1995, 19(2): 287-291. PMID: 7754637. DOI: 10.1007/BF00308640.
	Matsuda T, Tanaka H, Yuasa H, et al. The effects of high-dose vitamin C therapy on postburn lipid peroxidation[J]. J Burn Care Rehabil, 1993, 14(6): 624-629. PMID: 8300697. DOI: 10.1097/00004630-199311000-00007.