切换至 "中华医学电子期刊资源库"

第五届中国出版政府奖音像电子网络出版物奖提名奖

中国科技核心期刊

中国科学引文数据库(CSCD)来源期刊

中华重症医学电子杂志 ›› 2024, Vol. 10 ›› Issue (02) : 127 -135. doi: 10.3877/cma.j.issn.2096-1537.2024.02.006

专家论坛

脂质组学在急性呼吸窘迫综合征中的应用和临床进展
孙藏岚1, 黄丽丽1, 李小雨1, 邱海波1,()   
  1. 1. 210009 南京,江苏省重症医学重点实验室 东南大学附属中大医院重症医学科
  • 收稿日期:2023-07-03 出版日期:2024-05-28
  • 通信作者: 邱海波
  • 基金资助:
    国家自然科学基金重点项目(82341032); 科技部国家重点研发计划项目(2022YFC2504400)

Application and research progress of lipidomics in acute respiratory distress syndrome

Canglan Sun1, Lili Huang1, Xiaoyu Li1, Haibo Qiu1,()   

  1. 1. Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda hospital, School of Medicine, Southeast University, Nanjing 210009, China
  • Received:2023-07-03 Published:2024-05-28
  • Corresponding author: Haibo Qiu
引用本文:

孙藏岚, 黄丽丽, 李小雨, 邱海波. 脂质组学在急性呼吸窘迫综合征中的应用和临床进展[J]. 中华重症医学电子杂志, 2024, 10(02): 127-135.

Canglan Sun, Lili Huang, Xiaoyu Li, Haibo Qiu. Application and research progress of lipidomics in acute respiratory distress syndrome[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(02): 127-135.

急性呼吸窘迫综合征(ARDS)是以顽固性低氧血症为特征、严重威胁患者生命的肺部疾病。脂质组学是对生物、组织或细胞内脂质及与脂质相互作用的因素进行系统性分析的新兴学科,其在疾病发生及诊断中的作用受到越来越多的重视。近年来,许多基于脂质组学筛选出的代谢产物被提出可作为潜在的生物标志物,用于评估ARDS的早期发展及预后,并为新的靶向干预措施提供依据。本文对脂质组学在ARDS发病机制、诊断、异质性、预后及治疗中的应用进行综述。

Acute respiratory distress syndrome (ARDS) is a life-threatening lung disease characterized by intractable hypoxemia. Lipidomics is a new subject for systematic analysis of lipids in organisms, tissues or cells and factors interacting with lipids. More and more attention has been paid to its role in the occurrence and diagnosis of diseases. In recent years, many metabolites screened based on lipidomics have been proposed as potential biomarkers to evaluate the early development and prognosis of ARDS, and provide a basis for new targeted interventions. We reviewed the application of lipidomics in the pathogenesis, diagnosis, heterogeneity, prognosis and treatment of ARDS in this review.

图1 脂质代谢机制53 注:AA为花生四烯酸;ACC为乙酰辅酶a羧化酶;ACLY为ATP柠檬酸合成酶;AGPAT为1-酰基甘油-3-磷酸-O-酰基转移酶;ALA为α-亚麻酸;CD36为分化群36;DHA为二十二碳六烯酸;EPA为二十碳五烯酸;ELOVLs为极长链脂肪酸蛋白的延伸;FAs为脂肪酸;FABPs为脂肪酸结合蛋白;FAHFA为羟基脂肪酸酯;FATPs为脂肪酸转运蛋白;G3P为3-磷酸甘油酯;LA为亚油酸;MUFA为单不饱和脂肪酸;PA为磷脂酸;PPP为磷酸戊糖途径;R5P为5-磷酸核糖;SPM为专门的促解介质;橘色箭头代表脂类的合成代谢途径;灰色箭头表示分解代谢途径
图2 脂质组学工作流程54 注:MTBE为甲基叔丁基醚;SPE为固相萃取;LC-MS为液相色谱-质谱法;HILIC为亲水相互作用色谱;DIMS为直接进样质谱技术;DTIMST为漂移时间离子迁移率光谱法;WIMS为全信息化精益管理软件;MALDI为基质辅助激光解吸离子化技术;SIMS为针对质谱技术;MALDI-TOF为基质辅助激光解吸电离飞行时间质谱;OzID为臭氧诱导解离;EIEIO为有机离子的电子冲击激发
表1 ARDS脂质组学研究
文献 年份(年) 研究目的 研究对象 实验组人群及样本量 对照组人群及样本量 样本类型 分析平台 ARDS相关脂质代谢物
Seeds等[33] 2012 ARDS发病机制 ARDS患者(18例) 健康对照者(10例) BALF HPLC-ELSD 分泌型磷脂酶、前列腺素
Dushianthan等[34] 2014 ARDS发病机制 ARDS患者(10例) 健康对照者(10例) BALF ESI-MS 血浆磷脂酰胆碱
Dushianthan等[35] 2018 ARDS发病机制 ARDS患者(10例) 健康对照者(10例) 血浆 ESI-MS PC16:0_18:2、PUFA、甲基-D9-PC、甲基-D3-PC、甲基-D6-PC
Cotogni等[38] 2015 ARDS发病机制 ARDS患者(12例) - BALF LC-MS、GC-MS 前列腺素E2、花生四烯酸
Zhang等[39] 2017 ARDS发病机利 大鼠 PM2.5诱导的ALI/ARDS大鼠 - BALF UHPLC-MS/MS 鞘脂代谢物、游离脂肪酸
Evans等[40] 2014 ARDS诊断 ARDS患者(18例) 健康对照者(8例) BALF LC-MS 磷脂酰胆碱
Bos等[41] 2014 ARDS诊断 入ICU 24 h内进行机械通气的ARDS患者(42例) 入ICU 24 h内进行机械通气的非ARDS患者(59例) 呼出气 GC-MS 辛烷、乙醛、3-甲基庚烷
Stringer等[42] 2014 ARDS诊断 ARDS患者(14例) 非机械通气的脓零在患者(33例) 血清 H-NMR 总脂质、总亚甲基脂质和总胆碱水平
Rogers等[43] 2017 ARDS诊断 ARDS患者(16例) 静水性肺水肿患者(13例) 肺水肿液 UHPLC-MS/MS 1/3的ARDS患者中脂质代谢物水平显著升高
Xu等[44] 2020 ARDS诊断 ARDS患者(42例) 健康对照者(28例) 血浆 UHPLC-MS/MS 1-亚油酰甘油胆碱、PC(16,0/0:0)、磷脂酰胆碱溶酶18:2、LysoPC20:4(5Z,8Z,11Z,14Z)
Aipanah等[45] 2023 ARDS异质性 ARDS高炎症表型患者(35例) ARDS低炎在表型患者(58例) 血浆 UHPLC-MS/MS 循环亚油酸(LA,多不饱和脂肪酸-6系列)、花生四烯酸、二十碳五烯酸(EPA)、二十二联六烯酸(DHA)
Viswan等[46] 2019 ARDS异质性 ARDS.患者 择期手术的机械通气患者 血清、mBALF H-NMR
严重程度:血清(176例)mBALF(146例) 血清(68例)mBALF(40例)
异质性:血清(147例)mBALF(128例)
Yan等[47] 2022 ARDS异质性 合并ARDS的CAP患者(43例) 未合并ARDS的CAP患者(45例) 血清、尿液 NMR 胆碱(AUC0.866)
Lorente等[48] 2021 ARDS异质性 COVID-19合并ARDS患者(18例) IAP合并ARDS患者(20例) 血清 HR-MAS NMR 甘油酯、甘油磷脂、胆碱、游离多不饱和脂肪酸
Maile等[49] 2018 ARDS预后 ARDS患者死亡组(8例) ARDS患者存活组(22例) 血浆 LC-MS SM43:1,TG56:6,TG52:6、TG52:5
Xu等[44] 2020 ARDS预后 小鼠 注射苯丙氨酸ARDS小鼠 注射萃丙氨酸/PBS ARDS小鼠 血浆 UHPLC-MSMS d-苯丙氨酸、肉豆蔻酸、油酸
Tao等[50] 2022 ARDS治疗 大鼠 ARDS注射AEE组 ARDS对照组 血清 UHPLC-QTOF-MS/MS 髓过氧化物酶、丙二醛
Ross等[51] 2021 ARDS治疗 小鼠 注射流感病毒浓液ARDS小鼠 注射流感病毒稀释液ARDS小鼠 肺组织 ESI-MS 总磷脂酰胆碱、神经酰胺、磷脂酰肌醇、溶血磷脂、游离脂肪酸
Abdulnour等[52] 2018 ARDS治疗 ARDS患者阿司匹林组(184例) ARDS患者安慰剂组(183例) 血清 NMR 脂素A4(15-epi-LXA4)
1
Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries [J]. JAMA, 2016, 315(8): 788-800.
2
Bos LDJ, Ware LB. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes [J]. Lancet (London, England), 2022, 400(10358): 1145-1156.
3
Cioccari L, Luethi N, Masoodi M. Lipid mediators in critically ill patients: a step towards precision medicine [J]. Front Immunol, 2020, 11: 599853.
4
Yang K, Han X. Lipidomics: techniques, applications, and outcomes related to biomedical sciences [J]. Trends Biochem Sci, 2016, 41(11): 954-969.
5
Khaing P, Pandit P, Awsare B, et al. Pulmonary circulation in obesity, diabetes, and metabolic syndrome [J]. Compr Physiol, 2019, 10(1): 297-316.
6
Varela ML, Mogildea M, Moreno I, et al. Acute inflammation and metabolism [J]. Inflammation, 2018, 41(4): 1115-1127.
7
Glasser JR, Mallampalli RK. Surfactant and its role in the pathobiology of pulmonary infection [J]. Microbes Infect, 2012, 14(1): 17-25.
8
Griese M. Pulmonary surfactant in health and human lung diseases: state of the art [J]. Eur Respir J, 1999, 13(6): 1455-1476.
9
Numata M, Chu HW, Dakhama A, et al. Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus-induced inflammation and infection [J]. Proc Natl Acad Sci USA, 2010, 107(1): 320-325.
10
Perino J, Crouzier D, Spehner D, et al. Lung surfactant DPPG phospholipid inhibits vaccinia virus infection [J]. Antiviral Res, 2011, 89(1): 89-97.
11
Numata M, Kandasamy P, Nagashima Y, et al. Phosphatidylglycerol suppresses influenza A virus infection [J]. Am J Respir Cell Mol Biol, 2012, 46(4): 479-487.
12
Stables MJ, Gilroy DW. Old and new generation lipid mediators in acute inflammation and resolution [J]. Prog Lipid Res, 2011, 50(1): 35-51.
13
Pienkos SM, Moore AR, Guan J, et al. Effect of total cholesterol and statin therapy on mortality in ARDS patients: a secondary analysis of the SAILS and HARP-2 trials [J]. Crit Care, 2023, 27(1): 126.
14
Yang L, Luo Z, Shi X, et al. Different value of HDL-C in predicting outcome of ARDS secondary to bacterial and viral pneumonia: a retrospective observational study [J]. Heart Lung, 2021, 50(1): 206-213.
15
Han X, Gross RW. Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics [J]. J Lipid Res, 2003, 44(6): 1071-1079.
16
Fahy E, Subramaniam S, Brown HA, et al. A comprehensive classification system for lipids [J]. J Lipid Res, 2005, 46(5): 839-861.
17
Harkewicz R, Dennis EA. Applications of mass spectrometry to lipids and membranes [J]. Annu Rev Biochem, 2011, 80: 301-325.
18
Schex R, Lieb VM, Jiménez VM, et al. HPLC-DAD-APCI/ESI-MS(n) analysis of carotenoids and α-tocopherol in Costa Rican Acrocomia aculeata fruits of varying maturity stages [J]. Food Res Int, 2018, 105: 645-653.
19
Kühn C, Von Oesen T, Herz C, et al. In vitro determination of protein conjugates in human cells by LC-ESI-MS/MS after Benzyl Isothiocyanate exposure [J]. J Agric Food Chem, 2018, 66(26): 6727-6733.
20
Shao Y, Zhu B, Zheng R, et al. Development of urinary pseudotargeted LC-MS-based metabolomics method and its application in hepatocellular carcinoma biomarker discovery [J]. J Proteome Res, 2015, 14(2): 906-916.
21
Borisjuk L, Rolletschek H, Neuberger T. Nuclear magnetic resonance imaging of lipid in living plants [J]. Prog Lipid Res, 2013, 52(4): 465-487.
22
Li J, Vosegaard T, Guo Z. Applications of nuclear magnetic resonance in lipid analyses: an emerging powerful tool for lipidomics studies [J]. Prog Lipid Res, 2017, 68: 37-56.
23
Han X, Gross RW. Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples [J]. Mass Spectrom Rev, 2005, 24(3): 367-412.
24
Lin M, Wang Z, Wang D, et al. Mathematical model-assisted UHPLC-MS/MS method for global profiling and quantification of cholesteryl esters in hyperlipidemic golden hamsters [J]. Anal Chem, 2019, 91(7): 4504-4512.
25
Schlotterbeck J, Chatterjee M, Gawaz M, et al. Comprehensive MS/MS profiling by UHPLC-ESI-QTOF-MS/MS using SWATH data-independent acquisition for the study of platelet lipidomes in coronary artery disease [J]. Anal Chim Acta, 2019, 1046: 1-15.
26
Kim SH, Yang JS, Lee JC, et al. Lipidomic alterations in lipoproteins of patients with mild cognitive impairment and Alzheimer's disease by asymmetrical flow field-flow fractionation and nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry [J]. J Chromatogr A, 2018, 1568: 91-100.
27
Li Z, Guan M, Lin Y, et al. Aberrant lipid metabolism in hepatocellular carcinoma revealed by liver lipidomics [J]. Int J Mol Sci, 2017, 18(12): 2550.
28
Chen Y, Ma Z, Shen X, et al. Serum lipidomics profiling to identify biomarkers for non-small cell lung cancer [J]. Biomed Res Int, 2018, 2018: 5276240.
29
Yang R, Zhang Y, Qian W, et al. Surfactant lipidomics of alveolar lavage fluid in mice based on ultra-high-performance liquid chromatography coupled to hybrid quadrupole-exactive orbitrap mass spectrometry [J]. Metabolites, 2019, 9(4): 80.
30
Gika H, Virgiliou C, Theodoridis G, et al. Untargeted LC/MS-based metabolic phenotyping (metabonomics/metabolomics): the state of the art [J]. J Chromatogr B, Anal Technol Biomed life Sci, 2019, 1117: 136-147.
31
Mandal R, Chamot D, Wishart DS. The role of the human metabolome database in inborn errors of metabolism [J]. J Inherit Metab Dis, 2018, 41(3): 329-336.
32
Hallman M, Spragg R, Harrell JH, et al. Evidence of lung surfactant abnormality in respiratory failure. Study of bronchoalveolar lavage phospholipids, surface activity, phospholipase activity, and plasma myoinositol [J]. J Clin Invest, 1982, 70(3): 673-683.
33
Seeds MC, Grier BL, Suckling BN, et al. Secretory phospholipase A2-mediated depletion of phosphatidylglycerol in early acute respiratory distress syndrome [J]. Am J Med Sci, 2012, 343(6): 446-451.
34
Dushianthan A, Goss V, Cusack R, et al. Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome [J]. Respir Res, 2014, 15(1): 128.
35
Dushianthan A, Cusack R, Grocott MPW, et al. Abnormal liver phosphatidylcholine synthesis revealed in patients with acute respiratory distress syndrome [J]. J Lipid Res, 2018, 59(6): 1034-1045.
36
Nestel PJ. Fish oil and cardiovascular disease: lipids and arterial function [J]. Am J Clin Nutr, 2000, 71(1 Suppl): 228S-231S.
37
Urakaze M, Hamazaki T, Makuta M, et al. Infusion of fish oil emulsion: effects on platelet aggregation and fatty acid composition in phospholipids of plasma, platelets, and red blood cell membranes in rabbits [J]. Am J Clin Nutr, 1987, 46(6): 936-940.
38
Cotogni P, Trombetta A, Muzio G, et al. The Omega-3 Fatty Acid Docosahexaenoic Acid modulates inflammatory mediator release in human alveolar cells exposed to bronchoalveolar lavage fluid of ARDS Patients [J]. Biomed Res Int, 2015, 2015: 642520.
39
Zhang SY, Shao D, Liu H, et al. Metabolomics analysis reveals that benzo[a]pyrene, a component of PM (2.5), promotes pulmonary injury by modifying lipid metabolism in a phospholipase A2-dependent manner in vivo and in vitro [J]. Redox Biol, 2017, 13: 459-469.
40
Evans CR, Karnovsky A, Kovach MA, et al. Untargeted LC-MS metabolomics of bronchoalveolar lavage fluid differentiates acute respiratory distress syndrome from health [J]. J Proteome Res, 2014, 13(2): 640-649.
41
Bos LDJ, Weda H, Wang Y, et al. Exhaled breath metabolomics as a noninvasive diagnostic tool for acute respiratory distress syndrome [J]. Eur Respir J, 2014, 44(1): 188-197.
42
Stringer KA, Jones AE, Puskarich MA, et al. 1H-nuclear magnetic resonance (NMR)-detected lipids associated with apoptosis differentiate early acute respiratory distress syndrome (ARDS) from sepsis [J]. Am J Respir Crit Care Med, 2014, 189: A5000.
43
Rogers AJ, Contrepois K, Wu M, et al. Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset [J]. Am J Physiol Lung Cell Mol Physiol, 2017, 312(5): L703-L709.
44
Xu J, Pan T, Qi X, et al. Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine [J]. Respir Res, 2020, 21(1): 99.
45
Alipanah-Lechner N, Neyton L, Mick E, et al. Plasma metabolic profiling implicates dysregulated lipid metabolism and glycolytic shift in hyperinflammatory ARDS [J]. Am J Physiol Lung Cell Mol Physiol, 2023, 324(3): L297-L306.
46
Viswan A, Ghosh P, Gupta D, et al. Distinct metabolic endotype mirroring acute respiratory distress syndrome (ARDS) subphenotype and its heterogeneous biology [J]. Sci Rep, 2019, 9(1): 2108.
47
Yan Y, Chen J, Liang Q, et al. Metabolomics profile in acute respiratory distress syndrome by nuclear magnetic resonance spectroscopy in patients with community-acquired pneumonia [J]. Respir Res, 2022, 23(1): 172.
48
Lorente JA, Nin N, Villa P, et al. Metabolomic diferences between COVID-19 and H1N1 influenza induced ARDS [J]. Crit Care, 2021, 25(1): 390.
49
Maile MD, Standiford TJ, Engoren MC, et al. Associations of the plasma lipidome with mortality in the acute respiratory distress syndrome: a longitudinal cohort study [J]. Respir Res, 2018, 19(1): 60.
50
Tao Q, Zhang ZD, Qin Z, et al. Aspirin eugenol ester alleviates lipopolysaccharide-induced acute lung injury in rats while stabilizing serum metabolites levels [J]. Front Immunol, 2022, 13: 939106.
51
Rosas LE, Doolittle LM, Joseph LM, et al. Postexposure liponucleotide prophylaxis and treatment attenuates acute respiratory distress syndrome in influenza-infected mice [J]. Am J Respir Cell Mol Biol, 2021, 64(6): 677-686.
52
Abdulnour RE, Gunderson T, Barkas I, et al. Early intravascular events are associated with development of acute respiratory distress syndrome. A substudy of the LIPS-A clinical trial [J]. Am J Respir Crit Care Med, 2018, 197(12): 1575-1585.
53
Jeon YG, Kim YY, Lee G, et al. Physiological and pathological roles of lipogenesis [J]. Nat Metab, 2023, 5(5): 735-759.
54
Züllig T, Trötzmüller M, Köfeler HC. Lipidomics from sample preparation to data analysis: a primer [J]. Anal Bioanal Chem, 2020, 412(10): 2191-2209.
[1] 董道然, 宗媛, 王艳, 荆程桥, 任嘉伟. 右心保护性通气策略在急性呼吸窘迫综合征患者中的应用:一项前瞻性随机对照研究[J]. 中华危重症医学杂志(电子版), 2023, 16(06): 461-468.
[2] 许媛媛, 赵悦岐, 李雪, 曲燕. 艾灸在病毒疣中的临床应用及其机制研究进展[J]. 中华实验和临床感染病杂志(电子版), 2023, 17(06): 390-394.
[3] 庞丹, 孙刚, 伊乐, 丁立云, 钟美艳, 张杰, 于婷婷, 郭乐峰. 血清HIF-1α、VEGF、Flt-1的检测对ARDS的预后及临床意义[J]. 中华肺部疾病杂志(电子版), 2024, 17(01): 127-130.
[4] 刘珂, 张婧娴, 王如刚. 肺超声纹理特征ARDS与心源性肺水肿的鉴别诊断意义[J]. 中华肺部疾病杂志(电子版), 2023, 16(06): 892-894.
[5] 刘悦, 潘纯. 急性呼吸窘迫综合征患者肌松剂滴定的必要性与可行性[J]. 中华重症医学电子杂志, 2024, 10(02): 108-112.
[6] 王永广, 朱鹏, 许千金, 甘桂芬, 石钟山, 潘纯. 急性呼吸窘迫综合征诊断标准亟需更新[J]. 中华重症医学电子杂志, 2024, 10(02): 113-117.
[7] 史楠, 袁雪燕, 邱海波. 肺复张在急性呼吸窘迫综合征中的应用和临床进展[J]. 中华重症医学电子杂志, 2024, 10(02): 118-126.
[8] 王晶晶, 谢晖, 邓璞钰, 张晨晨, 田学, 谢云, 王瑞兰. 新型冠状病毒感染ARDS患者EIT监测下俯卧位通气成像的改变[J]. 中华重症医学电子杂志, 2024, 10(01): 31-37.
[9] 李浩南, 张煜彭, 付焱, 冯继伟, 刘凯, 张文凯. 缝隙连接蛋白43在肺部疾病中的研究进展[J]. 中华重症医学电子杂志, 2024, 10(01): 60-65.
[10] 卢梦诗, 刘威, 马加威, 嵇丹丹, 贾璇, 詹心萍, 罗亮. 人工智能在急性呼吸窘迫综合征领域的应用进展[J]. 中华重症医学电子杂志, 2024, 10(01): 66-71.
[11] 陈含冰, 储翠林, 邱海波. 急性呼吸窘迫综合征中巨噬细胞死亡方式的研究进展[J]. 中华重症医学电子杂志, 2024, 10(01): 79-84.
[12] 戚泽雪, 赵连晖, 王广川, 张春清. 从国内专家共识推荐意见更新探讨经颈静脉肝内门体分流术的临床应用进展[J]. 中华消化病与影像杂志(电子版), 2024, 14(03): 193-196.
[13] 王吉, 张颖, 顾雪, 杨朋磊, 陈齐红. 间充质干细胞微泡对ARDS肺纤维化影响的实验研究[J]. 中华临床医师杂志(电子版), 2024, 18(01): 72-78.
[14] 王睿浩, 姜云璐, 田艳君. Apelin/APJ系统生理病理作用的研究进展[J]. 中华诊断学电子杂志, 2024, 12(02): 138-142.
[15] 计超, 向群. 乙酰胆碱受体对急性呼吸窘迫综合征小鼠T细胞亚群和炎症因子的影响[J]. 中华诊断学电子杂志, 2024, 12(01): 50-56.
阅读次数
全文


摘要