高血压特征代谢物组研究进展及其在中医证候分型中的应用
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摘要
高血压是最常见的慢性非传染性疾病,是心血管疾病的主要危险因素。已有研究表明,代谢紊乱是现代高血压病发病的重要环节。代谢组学作为检测体内代谢物的技术之一,可以反应不同状态下体内代谢物组水平的变化,已应用于探索高血压诊断、预防和治疗的生物标志物。同时,中医对于高血压进行辨证论治和整体治疗是高血压中医诊疗的特色。本文首先综述了高血压特征性代谢物组研究进展,并对利用代谢组学技术在高血压证候分型中的应用也进行了介绍,以期为高血压证候研究提供现代科学基础。
Hypertension is the most common chronic non-communicable disease and is a major risk factor for cardiovascular disease. Researches show that the metabolic disorder is a significant cause of hypertension. The in vivo metabolites detecting technique and metabonomics can be used to reflect the metabolites levels in different states of body. Therefore, metabonomics has been applied as biomarkers for early diagnosis, prevention, and treatment of hypertension. Treatment based on syndrome differentiation and holistic treatments are characteristics of the traditional Chinese medicine(TCM) diagnosis and treatment. This article reviews the advances in the study of characteristic metabolites in hypertension, and introduces the use of metabonomics techniques in the classification of hypertension syndrome to provide a modern scientific basis for hypertension syndrome research.Hypertension is the most common chronic non-communicable disease and is a major risk factor for cardiovascular disease. Researches show that the metabolic disorder is a significant cause of hypertension. The in vivo metabolites detecting technique and metabonomics can be used to reflect the metabolites levels in different states of body. Therefore,metabonomics has been applied as biomarkers for early diagnosis,prevention,and treatment of hypertension. Treatment based on syndrome differentiation and holistic treatments are characteristics of the traditional Chinese medicine( TCM) diagnosis and treatment. This article reviews the advances in the study of characteristic metabolites in hypertension,and introduces the use of metabonomics techniques in the classification of hypertension syndrome to provide a modern scientific basis for hypertension syndrome research.
Hypertension is the most common chronic non-communicable disease and is a major risk factor for cardiovascular disease. Researches show that the metabolic disorder is a significant cause of hypertension. The in vivo metabolites detecting technique and metabonomics can be used to reflect the metabolites levels in different states of body. Therefore, metabonomics has been applied as biomarkers for early diagnosis, prevention, and treatment of hypertension. Treatment based on syndrome differentiation and holistic treatments are characteristics of the traditional Chinese medicine(TCM) diagnosis and treatment. This article reviews the advances in the study of characteristic metabolites in hypertension, and introduces the use of metabonomics techniques in the classification of hypertension syndrome to provide a modern scientific basis for hypertension syndrome research.Hypertension is the most common chronic non-communicable disease and is a major risk factor for cardiovascular disease. Researches show that the metabolic disorder is a significant cause of hypertension. The in vivo metabolites detecting technique and metabonomics can be used to reflect the metabolites levels in different states of body. Therefore,metabonomics has been applied as biomarkers for early diagnosis,prevention,and treatment of hypertension. Treatment based on syndrome differentiation and holistic treatments are characteristics of the traditional Chinese medicine( TCM) diagnosis and treatment. This article reviews the advances in the study of characteristic metabolites in hypertension,and introduces the use of metabonomics techniques in the classification of hypertension syndrome to provide a modern scientific basis for hypertension syndrome research.
引文
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[7]孙静云, 顾赛红, 周仲瑛, 等. "证"的研究中几个重要问题的反思与展望. 中医杂志, 2014,(14)∶1171～1175.
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[9]Yang M, Yu Z, Deng S, et al. A Targeted Metabolomics MRM-MS Study on Identifying Potential Hypertension Biomarkers in Human Plasma and Evaluating Acupuncture Effects. Sci Rep, 2016,(6)∶25871.
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[13]蒋海强, 聂磊, 李运伦, 等. 高血压病肝阳上亢证尿液代谢组学气相色谱-质谱联用研究. 中国实验方剂学杂志, 2011,(11)∶138～142.
[14]van Deventer C A, Lindeque J Z, van Rensburg P J, et al. Use of metabolomics to elucidate the metabolic perturbation associated with hypertension in a black South African male cohort: the SABPA study. J Am Soc Hypertens, 2015,9(2)∶104～114.
[15]Zhao H, Liu Y, Li Z, et al. Identification of essential hypertension biomarkers in human urine by non-targeted metabolomics based on UPLC-Q-TOF/MS. Clin Chim Acta, 2018,486∶192～198.
[16]Derkach A, Sampson J, Joseph J, et al. Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)-Sodium Feeding Study. Am J Clin Nutr, 2017,106(4)∶1131～1141.
[17]Ameta K, Gupta A, Kumar S, et al. Essential hypertension: A filtered serum based metabolomics study. Sci Rep, 2017,7(1)∶2153.
[18]Bai Q, Peng B, Wu X, et al. Metabolomic study for essential hypertension patients based on dried blood spot mass spectrometry approach. IUBMB Life, 2018.
[19]Wang L, Hou E, Wang L, et al. Reconstruction and analysis of correlation networks based on GC-MS metabolomics data for young hypertensive men. Anal Chim Acta, 2015,854∶95～105.
[20]Zhong L, Zhang J P, Nuermaimaiti A G, et al. Study on plasmatic metabolomics of Uygur patients with essential hypertension based on nuclear magnetic resonance technique. Eur Rev Med Pharmacol Sci, 2014,18(23)∶3673～3680.
[21]Walejko J M, Kim S, Goel R, et al. Gut microbiota and serum metabolite differences in African Americans and White Americans with high blood pressure. Int J Cardiol, 2018.
[22]Stamler J, Elliott P, Dennis B, et al. INTERMAP: background, aims, design, methods, and descriptive statistics (nondietary). J Hum Hypertens, 2003,17(9)∶591～608.
[23]Ruiz-Ramirez A, Ortiz-Balderas E, Cardozo-Saldana G, et al. Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clin Sci (Lond), 2014,126(1)∶19～29.
[24]郑易, 史习宝, 胡海雷. 尿液儿茶酚胺水平与高血压控制水平的相关性. 心脑血管病防治, 2017,(6)∶480～482.
[25]Wang L, Hou E, Wang L, et al. Reconstruction and analysis of correlation networks based on GC-MS metabolomics data for young hypertensive men. Anal Chim Acta, 2015,854∶95～105.
[26]Kim M, Jung S, Kim S Y, et al. Prehypertension-associated elevation in circulating lysophosphatidlycholines, Lp-PLA2 activity, and oxidative stress. PLoS One, 2014,9(5)∶e96735.
[27]Zheng Y, Yu B, Alexander D, et al. Associations between metabolomic compounds and incident heart failure among African Americans: the ARIC Study. Am J Epidemiol, 2013,178(4)∶534～542.
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[29]蒋海强, 聂磊, 李运伦. 气质联用技术检测高血压病肝阳上亢证患者与健康志愿者血清脂肪酸成分的差异. 辽宁中医杂志, 2011,(6)∶1052～1054.
[30]高扬, 胡元会, 杨正, 等. 高血压病肝火亢盛证血清代谢组学初步研究. 国际中医中药杂志, 2013,(10)∶889～892.
[31]Steinberg H O, Tarshoby M, Monestel R, et al. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest, 1997,100(5)∶1230～1239.
[32]蒋海强, 李运伦, 解君. 基于高效液相色谱-电喷雾-飞行时间质谱联用技术的高血压病血浆代谢组学分析. 山东大学学报(医学版), 2011,(10)∶150～154.
[33]Au A, Cheng K K, Wei L K. Metabolomics, Lipidomics and Pharmacometabolomics of Human Hypertension. Adv Exp Med Biol, 2017,956∶599～613.
[34]Dietrich S, Floegel A, Weikert C, et al. Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation into Cancer and Nutrition-Potsdam Study. Hypertension, 2016,68(2)∶471～477.
[35]Kulkarni H, Meikle P J, Mamtani M, et al. Plasma lipidomic profile signature of hypertension in Mexican American families∶ specific role of diacylglycerols. Hypertension, 2013,62(3)∶621～626.
[36]Feng X, Yang Z, Chu Y, et al. 1H nuclear magnetic resonance-based metabolomic study on efficacy of Qingrehuatan decoction against abundant phlegm-heat syndrome in young adults with essential hypertension. J Tradit Chin Med, 2015,35(1)∶28～35.
[37]Hu C, Kong H, Qu F, et al. Application of plasma lipidomics in studying the response of patients with essential hypertension to antihypertensive drug therapy. Mol Biosyst, 2011,7(12)∶3271～3279.
[38]郑筱萸. 中药新药临床研究指导原则(试行).中国医药科技出版社,2002∶.
[39]蒋海强, 马斌, 聂磊, 等. 高血压病肝阳上亢证患者尿液样品的核磁共振谱代谢组学研究. 浙江中医药大学学报, 2011,(5)∶662～664.
[40]王宇,朱羽硕,李运伦,等. 正常高值血压肝火亢盛证分级量化诊断标准的探索性研究. 中华中医药杂志, 2018,(7)∶3035～3038.
[41]蒋海强, 李运伦. 高血压病肝阳上亢证代谢网络构建及特征分析. 世界科学技术-中医药现代化, 2013,(5)∶942～946.
[42]范群丽, 王广基, 阿基业, 等. 高血压病阴虚阳亢证的代谢组学内涵研究. 南京中医药大学学报, 2010,(6)∶409～411.
[43]朱嘉, 董海琪, 方祝元. 高血压病阴虚阳亢证的代谢组学研究. 深圳中西医结合杂志, 2013,(3)∶142～147.
[44]顾平, 张明雪. 镇肝熄风汤治疗阴虚阳亢型高血压的血浆代谢组学研究. 辽宁中医杂志, 2016,(7)∶1353～1355.
[45]冯玄超.清热化痰汤治疗青年原发性高血压痰热壅盛证的疗效及代谢组学研究.北京中医药大学,2012.
[46]吴天敏, 陈金水, 薛文娟, 等. 中青年高血压病痰湿壅盛证患者尿液代谢组学分析. 光明中医, 2016,(17)∶2458～2461.
[47]伍新诚, 郑景辉, 马晓聪, 等. 基于文献计量学的高血压痰湿壅盛证患者血浆代谢组学研究. 辽宁中医杂志, 2017,(7)∶1348～1355.
[48]贺玉泉, 李迪, 杨萍. 血清尿酸水平与高血压患者血管内皮功能的相关性研究. 中国实验诊断学, 2010,(8)∶1220～1222.
[49]陈艺, 方祝元. 高血压病肝火亢盛证与阴虚阳亢证的血清代谢组学比较研究. 南京中医药大学学报, 2013,(4)∶320～323.
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[51]陈玲珊,陈金水. 基于代谢组学高血压病"证"的本质研究. 中西医结合心脑血管病杂志, 2016,(2)∶140～142.
[52]Li Y, Nie L, Jiang H, et al. Metabonomics study of essential hypertension and its chinese medicine subtypes by using gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. Evid Based Complement Alternat Med, 2013,2013∶625906.
[2]Falaschetti E, Chaudhury M, Mindell J, et al. Continued improvement in hypertension management in England: results from the Health Survey for England 2006. Hypertension, 2009,53(3)∶480～486.
[3]Liu X, Gu W, Li Z, et al. Hypertension prevalence, awareness, treatment, control, and associated factors in Southwest China: an update. J Hypertens, 2017,35(3)∶637～644.
[4]刘巍, 熊兴江, 王阶. 高血压病代谢紊乱及化浊平肝法的临床运用. 中国中药杂志, 2013,(8)∶1251～1254.
[5]Dunn W B, Broadhurst D I, Atherton H J, et al. Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chem Soc Rev, 2011,40(1)∶387～426.
[6]李阳, 王莹, 郭琳. 高血压病代谢组学研究进展. 中华针灸电子杂志, 2014,(5)∶16～18.
[7]孙静云, 顾赛红, 周仲瑛, 等. "证"的研究中几个重要问题的反思与展望. 中医杂志, 2014,(14)∶1171～1175.
[8]Garcia-Puig J, Ruilope L M, Luque M, et al. Glucose metabolism in patients with essential hypertension. Am J Med, 2006,119(4)∶318～326.
[9]Yang M, Yu Z, Deng S, et al. A Targeted Metabolomics MRM-MS Study on Identifying Potential Hypertension Biomarkers in Human Plasma and Evaluating Acupuncture Effects. Sci Rep, 2016,(6)∶25871.
[10]Liu Y, Chen T, Qiu Y, et al. An ultrasonication-assisted extraction and derivatization protocol for GC/TOFMS-based metabolite profiling. Anal Bioanal Chem, 2011,400(5)∶1405～1417.
[11]宁澄, 王广基, 阿基业, 等. 高血压病肝火亢盛证型代谢组学的初步研究. 中西医结合心脑血管病杂志, 2015,(6)∶717～720.
[12]吴天敏, 陈金水, 薛文娟, 等. 中青年高血压病痰湿壅盛证患者血清样品代谢组学分析. 中国中医药信息杂志, 2016,(10)∶21～25.
[13]蒋海强, 聂磊, 李运伦, 等. 高血压病肝阳上亢证尿液代谢组学气相色谱-质谱联用研究. 中国实验方剂学杂志, 2011,(11)∶138～142.
[14]van Deventer C A, Lindeque J Z, van Rensburg P J, et al. Use of metabolomics to elucidate the metabolic perturbation associated with hypertension in a black South African male cohort: the SABPA study. J Am Soc Hypertens, 2015,9(2)∶104～114.
[15]Zhao H, Liu Y, Li Z, et al. Identification of essential hypertension biomarkers in human urine by non-targeted metabolomics based on UPLC-Q-TOF/MS. Clin Chim Acta, 2018,486∶192～198.
[16]Derkach A, Sampson J, Joseph J, et al. Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)-Sodium Feeding Study. Am J Clin Nutr, 2017,106(4)∶1131～1141.
[17]Ameta K, Gupta A, Kumar S, et al. Essential hypertension: A filtered serum based metabolomics study. Sci Rep, 2017,7(1)∶2153.
[18]Bai Q, Peng B, Wu X, et al. Metabolomic study for essential hypertension patients based on dried blood spot mass spectrometry approach. IUBMB Life, 2018.
[19]Wang L, Hou E, Wang L, et al. Reconstruction and analysis of correlation networks based on GC-MS metabolomics data for young hypertensive men. Anal Chim Acta, 2015,854∶95～105.
[20]Zhong L, Zhang J P, Nuermaimaiti A G, et al. Study on plasmatic metabolomics of Uygur patients with essential hypertension based on nuclear magnetic resonance technique. Eur Rev Med Pharmacol Sci, 2014,18(23)∶3673～3680.
[21]Walejko J M, Kim S, Goel R, et al. Gut microbiota and serum metabolite differences in African Americans and White Americans with high blood pressure. Int J Cardiol, 2018.
[22]Stamler J, Elliott P, Dennis B, et al. INTERMAP: background, aims, design, methods, and descriptive statistics (nondietary). J Hum Hypertens, 2003,17(9)∶591～608.
[23]Ruiz-Ramirez A, Ortiz-Balderas E, Cardozo-Saldana G, et al. Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Clin Sci (Lond), 2014,126(1)∶19～29.
[24]郑易, 史习宝, 胡海雷. 尿液儿茶酚胺水平与高血压控制水平的相关性. 心脑血管病防治, 2017,(6)∶480～482.
[25]Wang L, Hou E, Wang L, et al. Reconstruction and analysis of correlation networks based on GC-MS metabolomics data for young hypertensive men. Anal Chim Acta, 2015,854∶95～105.
[26]Kim M, Jung S, Kim S Y, et al. Prehypertension-associated elevation in circulating lysophosphatidlycholines, Lp-PLA2 activity, and oxidative stress. PLoS One, 2014,9(5)∶e96735.
[27]Zheng Y, Yu B, Alexander D, et al. Associations between metabolomic compounds and incident heart failure among African Americans: the ARIC Study. Am J Epidemiol, 2013,178(4)∶534～542.
[28]Zheng Y, Yu B, Alexander D, et al. Metabolomics and incident hypertension among blacks: the atherosclerosis risk in communities study. Hypertension, 2013,62(2)∶398～403.
[29]蒋海强, 聂磊, 李运伦. 气质联用技术检测高血压病肝阳上亢证患者与健康志愿者血清脂肪酸成分的差异. 辽宁中医杂志, 2011,(6)∶1052～1054.
[30]高扬, 胡元会, 杨正, 等. 高血压病肝火亢盛证血清代谢组学初步研究. 国际中医中药杂志, 2013,(10)∶889～892.
[31]Steinberg H O, Tarshoby M, Monestel R, et al. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest, 1997,100(5)∶1230～1239.
[32]蒋海强, 李运伦, 解君. 基于高效液相色谱-电喷雾-飞行时间质谱联用技术的高血压病血浆代谢组学分析. 山东大学学报(医学版), 2011,(10)∶150～154.
[33]Au A, Cheng K K, Wei L K. Metabolomics, Lipidomics and Pharmacometabolomics of Human Hypertension. Adv Exp Med Biol, 2017,956∶599～613.
[34]Dietrich S, Floegel A, Weikert C, et al. Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation into Cancer and Nutrition-Potsdam Study. Hypertension, 2016,68(2)∶471～477.
[35]Kulkarni H, Meikle P J, Mamtani M, et al. Plasma lipidomic profile signature of hypertension in Mexican American families∶ specific role of diacylglycerols. Hypertension, 2013,62(3)∶621～626.
[36]Feng X, Yang Z, Chu Y, et al. 1H nuclear magnetic resonance-based metabolomic study on efficacy of Qingrehuatan decoction against abundant phlegm-heat syndrome in young adults with essential hypertension. J Tradit Chin Med, 2015,35(1)∶28～35.
[37]Hu C, Kong H, Qu F, et al. Application of plasma lipidomics in studying the response of patients with essential hypertension to antihypertensive drug therapy. Mol Biosyst, 2011,7(12)∶3271～3279.
[38]郑筱萸. 中药新药临床研究指导原则(试行).中国医药科技出版社,2002∶.
[39]蒋海强, 马斌, 聂磊, 等. 高血压病肝阳上亢证患者尿液样品的核磁共振谱代谢组学研究. 浙江中医药大学学报, 2011,(5)∶662～664.
[40]王宇,朱羽硕,李运伦,等. 正常高值血压肝火亢盛证分级量化诊断标准的探索性研究. 中华中医药杂志, 2018,(7)∶3035～3038.
[41]蒋海强, 李运伦. 高血压病肝阳上亢证代谢网络构建及特征分析. 世界科学技术-中医药现代化, 2013,(5)∶942～946.
[42]范群丽, 王广基, 阿基业, 等. 高血压病阴虚阳亢证的代谢组学内涵研究. 南京中医药大学学报, 2010,(6)∶409～411.
[43]朱嘉, 董海琪, 方祝元. 高血压病阴虚阳亢证的代谢组学研究. 深圳中西医结合杂志, 2013,(3)∶142～147.
[44]顾平, 张明雪. 镇肝熄风汤治疗阴虚阳亢型高血压的血浆代谢组学研究. 辽宁中医杂志, 2016,(7)∶1353～1355.
[45]冯玄超.清热化痰汤治疗青年原发性高血压痰热壅盛证的疗效及代谢组学研究.北京中医药大学,2012.
[46]吴天敏, 陈金水, 薛文娟, 等. 中青年高血压病痰湿壅盛证患者尿液代谢组学分析. 光明中医, 2016,(17)∶2458～2461.
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