基于代谢组学的慢性心衰病证诊断研究述评
钟森杰 李静 李琳 黄淑敏 杨梦 邱宏 程彬 胡志希
湖南中医药大学中医诊断研究所,湖南长沙 410208
Review of the diagnosis of chronic heart failure syndrome based on metabonomics
ZHONG Senjie LI Jing LI Lin HUANG Shumin YANG Meng QIU Hong CHENG Bin HU Zhixi
Diagnostic Institute of Traditional Chinese Medicine, Hu′nan University of Chinese Medicine, Hu′nan Province, Changsha 410208, China
摘要 慢性心衰的病理过程中伴随着一系列代谢功能的复杂改变,代谢组学通过先进的检测技术与统计算法,可以从整体层面把握机体的代谢功能改变情况,现已成为心衰实验研究的常用手段。本文归纳总结代谢组学技术在慢性心衰病证诊断中的研究概况,基于“代谢性重构”理论阐述慢性心衰的代谢特征,探讨慢性心衰不同证候的代谢组学变化规律,认为代谢组学技术对心衰的病情评价及证型辨析具有一定的诊断价值。并对研究中存在的关键问题进行论述,提出规范统一研究标准、合理设计对照实验、注重心衰病证的动态过程研究等相应的思路,以期为后续研究提供借鉴。
关键词 :
慢性心衰 ,
代谢组学 ,
生物标志物 ,
诊断研究
Abstract :The pathological process of chronic heart failure is accompanied by a series of complex changes of metabolic function. Metabolomics can grasp the metabolic function changes of the body from the overall level through advanced detection technology and statistical algorithms, which has now become a common means of experimental research on heart failure. This article summarizes metabonomics technology in the diagnosis of chronic heart failure disease research, based on the theory of “metabolic remodeling”, the metabolic characteristics of chronic heart failure are expounded, and the metabonomics change rules of different syndromes of chronic heart failure are discussed. It is believed that metabonomics technology has certain diagnostic value for the assessment of heart failure and the discrimination of syndrome types of heart failure. In addition, the key problems in the study are discussed, and the corresponding ideas such as standardized and unified research standards, reasonable design of controlled experiments, and emphasis on the dynamic process research of heart failure syndrome are put forward, so as to provide reference for subsequent studies.
Key words :
Chronic heart failure
Metabolomics
Biomarkers
Diagnostic research
基金资助: 国家自然科学基金资助项目(81774208);
湖南省自然科学基金项目(2019JJ50447)。
通讯作者:
胡志希(1962-),男,博士,教授,博士生导师;研究方向:心血管疾病生物学基础研究。
作者简介 : 钟森杰(1993-),男,湖南中医药大学2019级中医诊断学专业在读博士研究生;研究方向:心血管疾病生物学基础研究。
[1] 陈可冀,吴宗贵,朱明军,等.慢性心力衰竭中西医结合诊疗专家共识[J].中国中西医结合杂志,2016,36(2):133-141.
[2] Metra M,Teerlink JR. Heart failure [J]. Lancet,2017,390(10106):1981-1995.
[3] 魏峰,张松林,张玉顺,等.心力衰竭生物学标志物的临床意义及研究进展[J].重庆医科大学学报,2018,43(3):311-316.
[4] Doehner W,Frenneaux M,Anker SD. Metabolic impairment in heart failure: the myocardial and systemic perspective [J]. J Am Coll Cardiol,2014,64(13):1388-1400.
[5] Albert CL,Tang WHW. Metabolic Biomarkers in Heart Failure [J]. Heart Fail Clin,2018,14(1):109-118.
[6] McGarrah RW,Crown SB,Zhang GF,et al. Cardiovascular Metabolomics [J]. Circ Res,2018,122(9):1238-1258.
[7] Chen L,Song J,Hu S. Metabolic remodeling of substrate utilization during heart failure progression [J]. Heart Fail Rev,2019,24(1):143-154.
[8] van Bilsen M,Smeets PJ,Gilde AJ,et al. Metabolic remodelling of the failing heart:the cardiac burn-out syndrome? [J]. Cardiovasc Res,2004,61(2):218-226.
[9] Tuomainen T,Tavi P. The role of cardiac energy metabolism in cardiac hypertrophy and failure [J]. Exp Cell Res,2017, 360(1):12-18.
[10] Bertero E,Maack C. Metabolic remodelling in heart failure [J]. Nat Rev Cardiol,2018,15(8):457-470.
[11] Jameel MN,Xiong Q,Mansoor A,et al. ATP sensitive K(+) channels are critical for maintaining myocardial perfusion and high energy phosphates in the failing heart [J]. J Mol Cell Cardiol,2016,92:116-121.
[12] Mahmod M,Pal N,Rayner J,et al. The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction:a cardiovascular magnetic resonance study [J]. J Cardiovasc Magn Reson,2018,20(1):88.
[13] 李楠.调节底物代谢对衰竭心肌代谢重构的干预作用及相关机制研究[D].重庆:第三军医大学,2010.
[14] Noordali H,Loudon BL,Frenneaux MP,et al. Cardiac metabolism - A promising therapeutic target for heart failure [J]. Pharmacol Ther,2018,182(2):95-114.
[15] Peterzan MA,Lygate CA,Neubauer S,et al. Metabolic remodeling in hypertrophied and failing myocardium:a review [J]. Am J Physiol Heart Circ Physiol,2017,313(3):H597-H616.
[16] Doenst T,Nguyen TD,Abel ED. Cardiac metabolism in heart failure:implications beyond ATP production [J]. Circ Res,2013,113(6):709-724.
[17] 邱英茹,张瑞英.心肌代谢重构在慢性心力衰竭进展中的作用[J].心血管病学进展,2018,39(2):205-209.
[18] Hunter WG,Kelly JP,McGarrah RW 3rd,et al. Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction:Evidence for Shared Metabolic Impairments in Clinical Heart Failure [J]. J Am Heart Assoc,2016,5(8):e003190.
[19] Bedi KC Jr,Snyder NW,Brandimarto J,et al. Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure [J]. Circulation,2016,133(8):706-716.
[20] Lopaschuk GD,Ussher JR,Folmes CD,et al. Myocardial fatty acid metabolism in health and disease [J]. Physiol Rev,2010,90(1):207-258.
[21] 庞博,王斌,舒振波,等.慢性心功能衰竭患者尿液的代谢组学研究[J].分析化学,2017,45(8):1165-1171.
[22] 谢雅革,沈克平,卢艳琳,等.基于代谢组学的中医血瘀证研究概述[J].中华中医药杂志,2019,34(6):2598-2601.
[23] 杨梦,胡思远,胡志希,等.基于“虚气留滞”理论探讨慢性心力衰竭的发病机理[J].环球中医药,2019,12(12):1779-1782.
[24] 李琪琳,张安晶,吴华芹,等.基于~1H-NMR技术研究心气虚证心力衰竭模型大鼠尿液代谢组学变化[J].北京中医药,2013,32(12):939-943.
[25] 李欣春,梁昊,胡志希,等.高血压心衰大鼠证候本质及药物干预研究[J].湖南中医药大学学报,2018,38(8):853-857.
[26] 钟森杰,李欣春,李杰,等.心气阴两虚证心力衰竭大鼠血浆代谢组学研究[J].湖南中医药大学学报,2018,38(9):981-985.
[27] 曾瑞峰.基于反相高效液相的方法研究心衰心阳虚证患者血浆氨基酸指纹图谱[D].广州:广州中医药大学,2010.
[28] 梁国荣.心衰心阳虚证血浆氨基酸(缬、苯丙、异亮、亮氨酸)代谢指纹图谱研究[D].广州:广州中医药大学,2011.
[29] Wang J,Guo S,Fao K,et al. Plasma metabolomics combined with personalized diagnosis guided by Chinese medicine reveals subtypes of chronic heart failure [J]. Journal of Traditional Chinese Medical Sciences,2015,2(2):80-90.
[30] 刘玲玲.慢性心力衰竭气虚血瘀证和阳虚水停证的尿液代谢组学研究[D].北京:中国中医科学院,2014.
[31] 王鹏军.缺血性心力衰竭气虚血瘀证和阳虚水停证生物学基础及代谢组学研究[D].北京:中国中医科学院,2013.
[32] 王娟,赵慧辉,陈建新,等.慢性心力衰竭血瘀证患者血浆代谢物研究[J].北京中医药大学学报,2016,39(2):101-105.
[33] 王娟.慢性心力衰竭中医证候生物学诊断模式及代谢组学研究[D].北京:北京中医药大学,2012.
[34] 陈静.基于证候要素辨证治疗慢性心衰的临床疗效评价及代谢组学研究[D].北京:北京中医药大学,2016.
[35] McKirnan MD,Ichikawa Y,Zhang Z,et al. Metabolomic analysis of serum and myocardium in compensated heart failure after myocardial infarction [J]. Life Sci,2019, 221:212-223.
[36] Moreira da Silva Guimar?觔es S,de Souza Cruz WM,de Souza Weigert G,et al. Decompensated Chronic Heart Failure Reduces Plasma L-carnitine [J]. Arch Med Res,2018,49(4):278-281.
[37] 张玉婷.慢性心力衰竭的中医证候要素与心功能分级的关联性研究[D].成都:成都中医药大学,2018.
[38] 陶秀梅.“肾阳虚”模型及证候的代谢组学研究[D].上海:上海交通大学,2009.
[39] 郑海生,蒋健.基于代谢组学慢性心力衰竭肾阳虚证代谢模式的研究[J].中国中医基础医学杂志,2017,23(5):645-647,695.
[40] 赵琳琳,邱新建,李若梦,等.代谢组学在冠心病及中医证候中应用的研究进展[J].中国中西医结合杂志,2018, 38(9):1143-1147.
[41] Cops J,Haesen S,De Moor B,et al. Current animal models for the study of congestion in heart failure: an overview [J]. Heart Fail Rev,2019,24(3):387-397.
[42] Janssen PML,Elnakish MT. Modeling heart failure in animal models for novel drug discovery and development [J].Expert Opin Drug Discov,2019,14(4):355-363.
[43] 刘姬艳,江婷婷,李继承.中医证候研究中蛋白质组学技术的应用进展[J].中华中医药杂志,2016,31(1):196-199.
[44] 李思汉,李书楠,周福,等.关于中医证候动物模型研究的思考[J].中华中医药杂志,2019,34(8):3357-3361.
[45] Hunter WG,Kelly JP,McGarrah RW 3rd,et al. Metabolic Dysfunction in Heart Failure: Diagnostic,Prognostic,and Pathophysiologic Insights From Metabolomic Profiling [J]. Curr Heart Fail Rep,2016,13(3):119-131.
[1]
赵黎 李青松 缪晚虹. 代谢组学在眼科中的研究进展 [J]. 中国医药导报, 2020, 17(5): 41-45.
[2]
熊中奎1 郎娟2 王思本1. 胶质母细胞瘤的生物标志物研究进展 [J]. 中国医药导报, 2020, 17(4): 55-58.
[3]
杨妮1* 徐建良1,2* 盛国光2 肖明中1,2. 代谢组学在中药抗肝纤维化研究中的进展 [J]. 中国医药导报, 2020, 17(29): 33-36.
[4]
田莎莎1 杨晓鹏1 郭珲1,2. 微小RNA在糖尿病肾病中的研究进展 [J]. 中国医药导报, 2020, 17(27): 58-61.
[5]
江美芳 高崎 王丹丹. 基于LC-MS代谢组学技术在中药化学成分中的应用 [J]. 中国医药导报, 2020, 17(25): 133-136.
[6]
祁永华 孙晖 王喜军. 重度抑郁症的代谢组学生物标志物研究进展 [J]. 中国医药导报, 2020, 17(12): 49-52.
[7]
王东 李晶洁 吕书勤. 基于UPLC-HDMS方法对健脾化湿法干预脾虚湿盛证肝癌患者的血浆代谢组学研究 [J]. 中国医药导报, 2020, 17(12): 145-148.
[8]
许秋雯1 郭自强2. 慢性心力衰竭心功能评价方法现状分析 [J]. 中国医药导报, 2020, 17(10): 35-37,49.
[9]
汪白云1 杨柳2 刘国良2 朴成玉3 李庆伟2 薛慧2 刘斌2. 基于代谢网络技术的补阳还五汤对APP/PS1双转基因小鼠干预作用的研究 [J]. 中国医药导报, 2019, 16(8): 13-17.
[10]
刘德广 马红丽 王宇 高敬书 吴效科▲. 先兆流产治疗的研究进展 [J]. 中国医药导报, 2019, 16(5): 30-33.
[11]
樊雅青 张大庆. 动脉硬化与心血管疾病的研究进展 [J]. 中国医药导报, 2019, 16(30): 30-33,49.
[12]
强璐 王雨萌 裴婷婷. 唾液巨噬细胞迁移抑制因子水平与原发性干燥综合征的相关性研究 [J]. 中国医药导报, 2019, 16(28): 103-105,117.
[13]
杨波 杨强 张爱华 王喜军. 基于代谢组学技术的中医药研究进展 [J]. 中国医药导报, 2019, 16(24): 24-28.
[14]
贾岢卿 高燕 程晓 夏文华 闻颖. 代谢组学技术在2型糖尿病治疗中的应用进展 [J]. 中国医药导报, 2019, 16(24): 36-39.
[15]
郑蕊1,2 杜守颖1,3 刘宇2 郭瑞4. 基于代谢组学技术的清开灵软胶囊解热作用机制研究 [J]. 中国医药导报, 2019, 16(19): 34-38.