液相色谱-质谱联用结合化学计量学方法分析冠心病及冠心病合并高血压患者的代谢特征

引用本文: 杨丽娟, 丁筱雪, 任繁栋, 蔡芳, 付光辉, 任达兵, 易伦朝, 张宏. 液相色谱-质谱联用结合化学计量学方法分析冠心病及冠心病合并高血压患者的代谢特征[J]. 分析化学, 2021, 49(10): 1649-1656. doi: 10.19756/j.issn.0253-3820.201572 shu

Citation: YANG Li-Juan, DING Xiao-Xue, REN Fan-Dong, CAI Fang, FU Guang-Hui, REN Da-Bing, YI Lun-Zhao, ZHANG Hong. Liquid Chromatography-Mass Spectrometry Combined with Chemometric Methods to Analyze the Metabolic Characteristics of Patients with Coronary Heart Disease and Coronary Heart Disease with Hypertension[J]. Chinese Journal of Analytical Chemistry, 2021, 49(10): 1649-1656. doi: 10.19756/j.issn.0253-3820.201572 shu

液相色谱-质谱联用结合化学计量学方法分析冠心病及冠心病合并高血压患者的代谢特征

杨丽娟 ^1, ,
丁筱雪 ^2, ,
任繁栋 ^1, ,
蔡芳 ^1, ,
付光辉 ^3, ,
任达兵 ^1, ,
易伦朝 ^{1,
,} ,
张宏 ^{2,4,
,}

1.
昆明理工大学农业与食品学院, 昆明 650504;
2.
昆明理工大学附属医院云南省第一人民医院心血管内科, 昆明 650032;
3.
昆明理工大学理学院, 昆明 650504;
4.
昆明理工大学生命科学院, 昆明 650504

通讯作者: 易伦朝,E-mail:yilunzhao@kust.edu.cn; 张宏,E-mail:zhkhzx@yeah.net

基金项目:
国家自然科学基金项目（No.21775058）和云南省应用基础研究项目（昆医联合专项）（No.2017FE468（-169））资助。

摘要: 以51例健康人、21例冠心病患者以及16例冠心病合并高血压患者的血浆为样本，采用超高效液相色谱-高分辨质谱联用技术，分析两类患者的血浆代谢特征。在定性和定量分析104个内源性代谢物的基础上，进行主成分分析、偏最小二乘-判别分析，并结合变量重要性投影与单因素方差分析，分别筛选出8、41和26种可区分健康人与冠心病患者、健康人与冠心病合并高血压患者、冠心病与冠心病合并高血压患者的潜在特征代谢物。代谢通路分析结果表明，在冠心病与冠心病合并高血压患者中，亚油酸等脂肪酸代谢途径以及苯丙氨酸、酪氨酸、色氨酸的生物合成等氨基酸代谢途径发生了明显变化。其中，氨基酸代谢在冠心病合并高血压患者中表现出更加显著的变化。

关键词:

English

Liquid Chromatography-Mass Spectrometry Combined with Chemometric Methods to Analyze the Metabolic Characteristics of Patients with Coronary Heart Disease and Coronary Heart Disease with Hypertension

1.
Faculty of Agriculture and Food, Kunming University of Science and Technology, Kunming 650504, China;
2.
Department of Cardiology, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China;
3.
Faculty of Science, Kunming University of Science and Technology, Kunming 650504, China;
4.
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650504, China

Corresponding author: YI Lun-Zhao, ; ZHANG Hong,

Received Date: 23 September 2020
Revised Date: 02 August 2021
Fund Project:
Supported by the National Natural Science Foundation of China (No.21775058) and the Yunnan Provincial Applied Basic Research Project (Kun Medical Joint Project) (No.2017FE468(-169)).

Abstract: Coronary heart disease with hypertension (CHD-HTN) is a serious threat to the life and health of patients. In this study, the plasma samples of 51 healthy controls, 21 patients with coronary heart disease (CHD) and 16 patients with CHD-HTN were used as samples, and the ultra-performance liquid chromatography-high resolution mass spectrometer was used to analyze the plasma metabolic characteristics of the two types of patients. Among them, 104 endogenous metabolites were analyzed qualitatively and quantitatively. On this basis, principal component analysis and partial least square-discriminant analysis models were established, and combined with the results of variable importance projection and one-way analysis of variance, 8, 41 and 26 characteristic metabolites were selected to distinguish between healthy controls and patients with CHD, healthy controls and patients with CHD-HTN, patients with CHD and CHD-HTN. The results of metabolic pathway analysis showed that in patients with CHD and CHD-HTN, significant changes took place in the metabolic pathways of fatty acids such as linoleic acid, as well as the biosynthesis of amino acids such as phenylalanine, tyrosine and tryptophan. Among them, amino acid metabolism showed more significant changes in patients with CHD-HTN.

Key words:

Coronary heart disease
/ Coronary heart disease with hypertension
/ Ultra-performance liquid chromatography-high resolution mass spectrometry
/ Metabonomics
/ Chemometrics

1. [1]
  LI H Y, SUN K, ZHAO R P, HU J, HAO Z R, WANG F, LU Y J, LIU F, ZHANG Y. Front. Biosci., 2017, 22:504-515.LI H Y, SUN K, ZHAO R P, HU J, HAO Z R, WANG F, LU Y J, LIU F, ZHANG Y. Front. Biosci., 2017, 22:504-515.
2. [2]
  HU Sheng-Shou, GAO Run-Lin, LIU Li-Sheng, ZHU Man-Lu, WANG Wen, WANG Yong-Jun, WU Zhao-Su, LI Hui-Jun, GU Dong-Feng, YANG Yue-Jin, ZHENG Zhe, CHEN Wei-Wei. Chin. Circul. J., 2019, 34(3):209-220. 胡盛寿, 高润霖, 刘力生, 朱曼璐, 王文, 王拥军, 吴兆苏, 李惠君, 顾东风, 杨跃进, 郑哲, 陈伟伟. 中国循环杂志, 2019, 34(3):209-220.
3. [3]
  AU A, CHENG K K, WEI L K. Adv. Exp. Med. Biol., 2017, 956:599-613.AU A, CHENG K K, WEI L K. Adv. Exp. Med. Biol., 2017, 956:599-613.
4. [4]
  CHAI Xiao-Rui, CUI Kai, YE Zhong-Ni. Chin. J. Geriatr. Heart, Brain Vessel Dis., 2016, 18(6):590-592. 柴晓芮, 崔凯, 叶中倪. 中华老年心脑血管病杂志, 2016, 18(6):590-592.
5. [5]
  FIEHN O, KOPKA J, DORMANN P, ALTMANN T, TRETHEWEY R N, WILLMITZER L. Nat. Biotechnol., 2000, 18(11):1157-1161.FIEHN O, KOPKA J, DORMANN P, ALTMANN T, TRETHEWEY R N, WILLMITZER L. Nat. Biotechnol., 2000, 18(11):1157-1161.
6. [6]
  NICHOLSON J K, CONNELLY J, LINDON J C, HOLMES E. Nat. Rev. Drug Discovery, 2002, 1(2):153-161.NICHOLSON J K, CONNELLY J, LINDON J C, HOLMES E. Nat. Rev. Drug Discovery, 2002, 1(2):153-161.
7. [7]
  CHENG S S, SHAH S H, CORWIN E J, FIEHN O, FITZGERALD R L, GERSZTEN R E, ILLIG T, RHEE E P, SRINIVAS P R, WANG T J, JAIN M. Circ.:Cardiovasc. Genet., 2017, 10(2):e000032.CHENG S S, SHAH S H, CORWIN E J, FIEHN O, FITZGERALD R L, GERSZTEN R E, ILLIG T, RHEE E P, SRINIVAS P R, WANG T J, JAIN M. Circ.:Cardiovasc. Genet., 2017, 10(2):e000032.
8. [8]
  LI Y P, ZHANG D, HE Y, CHEN C Z, SONG C X, ZHAO Y Y, BAI Y X, WANG Y, PU J L, CHEN J Z, YANG Y J, DOU K F. Sci. Rep., 2017, 7:15357.LI Y P, ZHANG D, HE Y, CHEN C Z, SONG C X, ZHAO Y Y, BAI Y X, WANG Y, PU J L, CHEN J Z, YANG Y J, DOU K F. Sci. Rep., 2017, 7:15357.
9. [9]
  PAYNTER N P, BALASUBRAMANIAN R, GIULIANINI F, WANG D D, TINKER L F, GOPAL S, DEIK A A, BULLOCK K, PIERCE K A, SCOTT J, MARTINEZ-GONZALEZ M A, ESTRUCH R, MANSON J E, COOKN R, ALBERT C M, CLISH C B, REXRODE K M. Circulation, 2018, 137(8):841-853.PAYNTER N P, BALASUBRAMANIAN R, GIULIANINI F, WANG D D, TINKER L F, GOPAL S, DEIK A A, BULLOCK K, PIERCE K A, SCOTT J, MARTINEZ-GONZALEZ M A, ESTRUCH R, MANSON J E, COOKN R, ALBERT C M, CLISH C B, REXRODE K M. Circulation, 2018, 137(8):841-853.
10. [10]
  BASAK T, VARSHNEY S, HAMID Z, GHOSH S, SETH S, SENGUPTA S. J. Proteomics, 2015, 127:169-177.BASAK T, VARSHNEY S, HAMID Z, GHOSH S, SETH S, SENGUPTA S. J. Proteomics, 2015, 127:169-177.
11. [11]
  WANG Y F, SUN W T, ZHENG J L, XU C, WANG X, LI T Y, TANG Y D, LI Z F. J. Chromatogr. B:Anal. Technol. Biomed. Life Sci., 2018, 1100:122-130.WANG Y F, SUN W T, ZHENG J L, XU C, WANG X, LI T Y, TANG Y D, LI Z F. J. Chromatogr. B:Anal. Technol. Biomed. Life Sci., 2018, 1100:122-130.
12. [12]
  TZOULAKI I, CASTAGNE R, BOULANGE C L, KARAMAN I, CHEKMENEVA E, EVANGELOU E, EBBELS T, KALUARACHCHI M R, CHADEAU-HYAM M, MOSEN D, DEHGHAN A, MOAYYERI A, FERREIRA D L S, GUO X Q, ROTTER J I, TAYLOR K D, KAVOUSI M, dE VRIES P S, LEHNE B, LOH M, HOFMAN A, NICHOLSON J K, CHAMBERS J, GIEGER C, HOLMES E, TRACY R, KOONER J, GREENLAND P, FRANCO O H, HERRINGTON D, LINDON J C, ELLIOTT P. Eur. Heart J., 2019, 40(34):2883-2896.TZOULAKI I, CASTAGNE R, BOULANGE C L, KARAMAN I, CHEKMENEVA E, EVANGELOU E, EBBELS T, KALUARACHCHI M R, CHADEAU-HYAM M, MOSEN D, DEHGHAN A, MOAYYERI A, FERREIRA D L S, GUO X Q, ROTTER J I, TAYLOR K D, KAVOUSI M, dE VRIES P S, LEHNE B, LOH M, HOFMAN A, NICHOLSON J K, CHAMBERS J, GIEGER C, HOLMES E, TRACY R, KOONER J, GREENLAND P, FRANCO O H, HERRINGTON D, LINDON J C, ELLIOTT P. Eur. Heart J., 2019, 40(34):2883-2896.
13. [13]
  FAN Y, LI Y, CHEN Y, ZHAO Y J, LIU L W, LI J, WANG S L, ALOLGA R N, YIN Y, WANG X M, ZHAO D S, SHEN J H, MENG F Q, ZHOU X, XU H, HE G P, LAI M D, LI P, ZHU W, QI L W. J. Am. Coll. Cardiol., 2016, 68(12):1281-1293.FAN Y, LI Y, CHEN Y, ZHAO Y J, LIU L W, LI J, WANG S L, ALOLGA R N, YIN Y, WANG X M, ZHAO D S, SHEN J H, MENG F Q, ZHOU X, XU H, HE G P, LAI M D, LI P, ZHU W, QI L W. J. Am. Coll. Cardiol., 2016, 68(12):1281-1293.
14. [14]
  KE C F, ZHU X H, ZHANG Y X, SHEN Y P. Metabolomics, 2018, 14(9):117.KE C F, ZHU X H, ZHANG Y X, SHEN Y P. Metabolomics, 2018, 14(9):117.
15. [15]
  ZHAO H, LIU Y J, LI Z, SONG Y Q, CAI X M, LIU Y C, ZHANG T P, YANG L, LI L, GAO S, LI Y B, YU C Q. Clin. Chim. Acta, 2018, 486:192-198.ZHAO H, LIU Y J, LI Z, SONG Y Q, CAI X M, LIU Y C, ZHANG T P, YANG L, LI L, GAO S, LI Y B, YU C Q. Clin. Chim. Acta, 2018, 486:192-198.
16. [16]
  MCGARRAH R W, CROWN S B, ZHANG G F, SHAH S H, NEWGARD C B. Circ. Res., 2018, 122(9):1238-1258.MCGARRAH R W, CROWN S B, ZHANG G F, SHAH S H, NEWGARD C B. Circ. Res., 2018, 122(9):1238-1258.
17. [17]
  LOPEZ-RUIZ R, ROMERO-GONZALEZ R, FRENICH A G. TrAC-Trends Anal. Chem., 2019, 118:170-181.LOPEZ-RUIZ R, ROMERO-GONZALEZ R, FRENICH A G. TrAC-Trends Anal. Chem., 2019, 118:170-181.
18. [18]
  MISRA B B. Metabolomics, 2021, 17(5):49.MISRA B B. Metabolomics, 2021, 17(5):49.
19. [19]
  XU T Y, ZHOU L, SHI Y Y, LIU L W, ZUO L H, JIA Q Q, DU S Z, KANG J, ZHANG X J, SUN Z. J. Biochem., 2018, 164(6):427-435.XU T Y, ZHOU L, SHI Y Y, LIU L W, ZUO L H, JIA Q Q, DU S Z, KANG J, ZHANG X J, SUN Z. J. Biochem., 2018, 164(6):427-435.
20. [20]
  YUAN X M, WEN J, JIA H W, TONG L, ZHAO J, ZHAO L S, XIONG Z L. Anal. Biochem., 2020, 591:113559.YUAN X M, WEN J, JIA H W, TONG L, ZHAO J, ZHAO L S, XIONG Z L. Anal. Biochem., 2020, 591:113559.
21. [21]
  GIKA H G, ZISI C, THEODORIDIS G, WILSON I D. J. Chromatogr. B:Anal. Technol. Biomed. Life Sci., 2016, 1008:15-25.GIKA H G, ZISI C, THEODORIDIS G, WILSON I D. J. Chromatogr. B:Anal. Technol. Biomed. Life Sci., 2016, 1008:15-25.
22. [22]
  CHONG J, WISHART D S, XIA J G. Curr. Protoc. Bioinf., 2019, 68(1):e86.CHONG J, WISHART D S, XIA J G. Curr. Protoc. Bioinf., 2019, 68(1):e86.
23. [23]
  WANG L L, LIU S, YANG W G, YU H T, ZHANG L, MA P, WU P, LI X, CHO K K, XUE S, JIANG B H. Sci. Rep., 2017, 7:40146.WANG L L, LIU S, YANG W G, YU H T, ZHANG L, MA P, WU P, LI X, CHO K K, XUE S, JIANG B H. Sci. Rep., 2017, 7:40146.
24. [24]
  CHEN G Y, SONG C W, JIN S N, LI S, ZHANG Y, HUANG R Z, FENG Y L, XU Y, XIANG Y, JIANG H L. Talanta, 2017, 162:530-539.CHEN G Y, SONG C W, JIN S N, LI S, ZHANG Y, HUANG R Z, FENG Y L, XU Y, XIANG Y, JIANG H L. Talanta, 2017, 162:530-539.
25. [25]
  GODZIEN J, CIBOROWSKI M, MARTINEZ-ALCAZAR M P, SAMCZUK P, KRETOWSKI A, BARBAS C. J. Proteome Res., 2015, 14(8):3204-3216.GODZIEN J, CIBOROWSKI M, MARTINEZ-ALCAZAR M P, SAMCZUK P, KRETOWSKI A, BARBAS C. J. Proteome Res., 2015, 14(8):3204-3216.
26. [26]
  YI L Z, DONG N P, YUN Y H, DENG B C, REN D B, LIU S, LIANG Y Z. Anal. Chim. Acta, 2016, 914:17-34.YI L Z, DONG N P, YUN Y H, DENG B C, REN D B, LIU S, LIANG Y Z. Anal. Chim. Acta, 2016, 914:17-34.
27. [27]
  GODZIEN J, CIBOROWSKI M, ANGULO S, BARBAS C. Electrophoresis, 2013, 34(19):2812-2826.GODZIEN J, CIBOROWSKI M, ANGULO S, BARBAS C. Electrophoresis, 2013, 34(19):2812-2826.
28. [28]
  REN Fan-Dong, DING Xiao-Xue, CAI Fang, REN Da-Bing, YI Lun-Zhao, ZHANG Hong. Chin. J. Anal. Chem., 2020, 48(1):49-56. 任繁栋, 丁筱雪, 蔡芳, 任达兵, 易伦朝, 张宏. 分析化学, 2020, 48(1):49-56.
29. [29]
  YI L Z, YUAN D L, CHE Z H, LIANG Y Z, ZHOU Z G, GAO H Y, WANG Y M. Metabolomics, 2008, 4(1):30-38.YI L Z, YUAN D L, CHE Z H, LIANG Y Z, ZHOU Z G, GAO H Y, WANG Y M. Metabolomics, 2008, 4(1):30-38.
30. [30]
  CAI F, REN F D, ZHANG Y M, DING X X, FU G H, REN D B, YANG L J, CHEN N, SHANG Y, HU Y D, YI L Z, ZHANG H. J. Chromatogr. B:Anal. Technol. Biomed. Life Sci., 2021, 1169:122603.CAI F, REN F D, ZHANG Y M, DING X X, FU G H, REN D B, YANG L J, CHEN N, SHANG Y, HU Y D, YI L Z, ZHANG H. J. Chromatogr. B:Anal. Technol. Biomed. Life Sci., 2021, 1169:122603.
31. [31]
  NITZ K, LACY M, ATZLER D. Arterioscler., Thromb., Vasc. Biol., 2019, 39(3):319-330.NITZ K, LACY M, ATZLER D. Arterioscler., Thromb., Vasc. Biol., 2019, 39(3):319-330.
32. [32]
  JENNINGS A, MACGREGOR A, WELCH A, CHOWIENCZYK P, SPECTOR T, CASSIDY A. J. Nutr., 2015, 145(9):2130-2138.JENNINGS A, MACGREGOR A, WELCH A, CHOWIENCZYK P, SPECTOR T, CASSIDY A. J. Nutr., 2015, 145(9):2130-2138.
33. [33]
  LIU G, CHEN S, ZHONG J, TENG K L, YIN Y L. Oxid. Med. Cell. Longevity, 2017, 2017:1602074.LIU G, CHEN S, ZHONG J, TENG K L, YIN Y L. Oxid. Med. Cell. Longevity, 2017, 2017:1602074.
34. [34]
  WANG F H, LIU J, DENG Q J, QI Y, WANG M, WANG Y, ZHANG X G, ZHAO D. Atherosclerosis, 2019, 286:7-13.WANG F H, LIU J, DENG Q J, QI Y, WANG M, WANG Y, ZHANG X G, ZHAO D. Atherosclerosis, 2019, 286:7-13.
35. [35]
  CHEN J N, ZHANGS L, WU J X, WU S Y, XU G S, WEI D H. DNA Cell Biol., 2020, 39(1):8-15.CHEN J N, ZHANGS L, WU J X, WU S Y, XU G S, WEI D H. DNA Cell Biol., 2020, 39(1):8-15.
36. [36]
  MIRMIRAN P, BAHADORAN Z, GHASEMI A, AZIZI F. Nutr., Metab. Cardiovasc. Dis., 2017, 27(7):633-641.MIRMIRAN P, BAHADORAN Z, GHASEMI A, AZIZI F. Nutr., Metab. Cardiovasc. Dis., 2017, 27(7):633-641.
37. [37]
  HUANG M N, ZHAO H, GAO S, LIU Y J, LIU Y C, ZHANG T P, CAI X M, LI Z, LI L, LI Y B, YU C Q. Clin. Chim. Acta, 2019, 497:95-103.HUANG M N, ZHAO H, GAO S, LIU Y J, LIU Y C, ZHANG T P, CAI X M, LI Z, LI L, LI Y B, YU C Q. Clin. Chim. Acta, 2019, 497:95-103.
38. [38]
  MONTEIRO J, LESLIE M, MOGHADASIAN M H, ARENDT B M, ALLARD J P, MA D W L. Food Funct., 2014, 5(3):426-435.MONTEIRO J, LESLIE M, MOGHADASIAN M H, ARENDT B M, ALLARD J P, MA D W L. Food Funct., 2014, 5(3):426-435.
39. [39]
  SONNWEBER T, PIZZINI A, NAIRZ M, WEISS G, TANCEVSKI I. Int. J. Mol. Sci., 2018, 19(11):3285.SONNWEBER T, PIZZINI A, NAIRZ M, WEISS G, TANCEVSKI I. Int. J. Mol. Sci., 2018, 19(11):3285.
40. [40]
  ZHAO Yin-Jiao, YAO Liu, ZHANG Xu, ZHU Yi. Chin. J. Arterioscler., 2020, 28(6):461-467. 赵银娇, 姚柳, 张栩, 朱毅. 中国动脉硬化杂志, 2020, 28(6):461-467.

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

液相色谱-质谱联用结合化学计量学方法分析冠心病及冠心病合并高血压患者的代谢特征

通讯作者: 易伦朝,E-mail:yilunzhao@kust.edu.cn; 张宏,E-mail:zhkhzx@yeah.net

English

Liquid Chromatography-Mass Spectrometry Combined with Chemometric Methods to Analyze the Metabolic Characteristics of Patients with Coronary Heart Disease and Coronary Heart Disease with Hypertension

Corresponding author: YI Lun-Zhao, ; ZHANG Hong,

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

液相色谱-质谱联用结合化学计量学方法分析冠心病及冠心病合并高血压患者的代谢特征

通讯作者: 易伦朝,E-mail:yilunzhao@kust.edu.cn; 张宏,E-mail:zhkhzx@yeah.net

English

Liquid Chromatography-Mass Spectrometry Combined with Chemometric Methods to Analyze the Metabolic Characteristics of Patients with Coronary Heart Disease and Coronary Heart Disease with Hypertension

Corresponding author: YI Lun-Zhao, ; ZHANG Hong,

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

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通讯作者: 陈斌, bchen63@163.com

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