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中国中医科学院 西苑医院,北京 100091
Received:18 March 2022,
Published Online:05 July 2022,
Published:05 January 2023
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王红芹,徐凤芹,周庆兵等.从“血气不和”理论探讨“代谢灵活性”失衡在糖尿病心肌病的作用[J].中国实验方剂学杂志,2023,29(01):194-201.
WANG Hongqin,XU Fengqin,ZHOU Qingbing,et al.Role of Imbalance of "Metabolic Flexibility" in Diabetic Cardiomyopathy: Based on Theory of “Blood-Qi Disharmony”[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(01):194-201.
王红芹,徐凤芹,周庆兵等.从“血气不和”理论探讨“代谢灵活性”失衡在糖尿病心肌病的作用[J].中国实验方剂学杂志,2023,29(01):194-201. DOI: 10.13422/j.cnki.syfjx.20221729.
WANG Hongqin,XU Fengqin,ZHOU Qingbing,et al.Role of Imbalance of "Metabolic Flexibility" in Diabetic Cardiomyopathy: Based on Theory of “Blood-Qi Disharmony”[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(01):194-201. DOI: 10.13422/j.cnki.syfjx.20221729.
糖尿病心肌病是独立于冠心病、高血压及其他危险因素情况下的心室功能障碍,可进展为心力衰竭。代谢灵活性失衡是导致糖尿病心肌病变的根本因素,其特点是营养感知扭曲、底物转换迟钝和能量平衡受损。糖尿病/胰岛素抵抗状态下,心脏脂肪酸氧化增加而葡萄糖氧化减少,使心脏代谢灵活性失衡,心脏不能根据条件变化(如进食/禁食、休息/运动)灵活转换底物,使心肌细胞能量生成减少,久之引起心脏功能障碍;另一方面,脂肪酸摄取过多超过了线粒体的
β
氧化能力,引起心脏脂质积聚,葡萄糖氧化减少使进入己糖胺生物合成途径及磷酸戊糖途径的葡萄糖增多,糖基化终产物生成增多,引起糖脂损伤作用,底物代谢异常的中间产物还会诱发氧化应激、炎症反应、线粒体功能障碍并进一步损伤心肌。气血是维持人体正常运行的主要功能物质,气血之间相互调和共同抵御邪气侵袭及其他应激事件,血气不和则会产生各种病理产物,导致疾病的发生。气血运行与物质代谢在功能及调控方面类似,气虚血瘀、气滞血瘀等“血气不和”贯穿整个糖尿病心肌病过程,“血气不和”会影响全身物质代谢进而导致机体能量代谢受损,通过系统阐释“血气不和”与“代谢灵活性”在糖尿病心肌病的关系,为益气活血中药通过靶向“代谢灵活性”防治糖尿病心肌病提供科学研究及临床组方思路。
Diabetic cardiomyopathy refers to dysfunction of cardiac muscle in patients with diabetes that cannot be directly ascribed to hypertension, coronary heart disease or other defined cardiac abnormalities. Imbalance in metabolic flexibility is the underlying cause of diabetic cardiomyopathy, which is manifested as distorted nutrient sensing, slow substrate switching, and impaired energy homeostasis. In the case of diabetes/insulin resistance, cardiac fatty acid oxidation increases while glucose oxidation decreases, resulting in the imbalance in cardiac metabolic flexibility. Thus, the heart fails to switch substrates depending on the changes (taking food/fasting, rest/exercise) and the energy production in cardiomyocytes reduced, causing cardiac dysfunction. Moreover, the excessive cardiac fatty acid fails to be degraded by the mitochondrial
β
oxidation, triggering cardiac lipid accumulation and reduction in glucose oxidation. Therefore, the glucose in the pentose phosphate (PPP) and the hexosamine biosynthetic pathway (HBP) increases and the production of advanced glycation end products rises, inducing glycolipotoxicity. The intermediates of abnormal substrate metabolism cause oxidative stress, inflammation, mitochondrial dysfunction and further result in impaired myocardial function. Qi and blood are the main functional substances for the normal functioning of the body. Qi and blood harmonize and work together to defend against external pathogen, while disharmony of blood and Qi will induce the production of various pathological products that lead to the occurrence of diseases. The function and regulation of Qi-Blood movement are similar to those of metabolism. Qi deficiency and blood stasis, Qi stagnation and blood stasis, and other "blood-Qi disharmony" types run through the whole process of diabetic cardiomyopathy, and "blood-Qi disharmony" will affect systemic substrate metabolism and lead to impaired energy metabolism. By systematically explaining the relationship between "blood-Qi disharmony" and "metabolic flexibility" in diabetic cardiomyopathy, we provide scientific research and clinical formulation ideas for targeting "metabolic flexibility" in the prevention of diabetic cardiomyopathy with Qi-replenishing and Blood-activating medicinals.
DAL CANTO E , CERIELLO A , RYDEN L , et al . Diabetes as a cardiovascular risk factor: An overview of global trends of macro and micro vascular complications [J]. Eur J Prev Cardiol , 2019 , 26 ( 2_suppl ): 25 - 32 .
LEE W S , KIM J . Diabetic cardiomyopathy: where we are and where we are going [J]. Korean J Intern Med , 2017 , 32 ( 3 ): 404 - 421 .
ARNOLD S V , ECHOUFFO-TCHEUGUI J B , LAM C S P , et al . Patterns of glucose-lowering medication use in patients with type 2 diabetes and heart failure. Insights from the diabetes collaborative registry (DCR) [J]. Am Heart J , 2018 , doi: 10.1016/j.ahj.2018.05.016 http://dx.doi.org/10.1016/j.ahj.2018.05.016 .
VARMA U , KOUTSIFELI P , BENSON V L , et al . Molecular mechanisms of cardiac pathology in diabetes - experimental insights [J]. Bba-Mol Basis Dis , 2018 , 1864 ( 5 ): 1949 - 1959 .
MUOIO D M . Metabolic inflexibility: When mito-chondrial indecision leads to metabolic gridlock [J]. Cell , 2014 , 159 ( 6 ): 1253 - 1262 .
KARWI Q G , SUN Q , LOPASCHUK G D . The contribution of cardiac fatty acid oxidation to diabetic cardiomyopathy severity [J]. Cells , 2021 , 10 ( 11 ): 3259 .
PASCUAL F , COLEMAN R A . Fuel availability and fate in cardiac metabolism: A tale of two substrates [J]. Biochim Biophys Acta , 2016 , 1861 ( 10 ): 1425 - 1433 .
刘姝璇 . 从肝论治糖尿病研究进展 [J]. 河南中医 , 2021 , 41 ( 12 ): 1939 - 1944 .
袁卫玲 , 苏玮莲 , 马佐英 . 论中医脾功能变化与糖脂代谢关系 [J]. 中国中医药信息杂志 , 2015 , 22 ( 10 ): 7 - 8 .
颜凯旋 , 华爽 , 吴小琴 . 基于新型代谢激素解析“枢纽肝”调节糖脂代谢的物质基础 [J]. 世界中医药 , 2019 , 14 ( 1 ): 18 - 21 .
黄艳丽 , 吕雄 , 张杰文 . 从气血不和理论探讨糖尿病糖脂代谢紊乱机理 [J]. 世界最新医学信息文摘 , 2017 , 17 ( 34 ): 157 - 158 .
陈丽超 , 刘彤 . 从虚、痰、瘀论治糖尿病心肌病 [J]. 实用中医内科杂志 , 2010 , 24 ( 7 ): 63 - 64 .
苏丽清 , 喻嵘 , 吴勇军 . 糖尿病心肌病从“久病入络”论治探讨 [J]. 湖南中医药大学学报 , 2017 , 37 ( 8 ): 838 - 841 .
GOODPASTER B H , SPARKS L M . Metabolic flexibility in health and disease [J]. Cell Metab , 2017 , 25 ( 5 ): 1027 - 1036 .
SMITH R L , SOETERS M R , WUST R C I , et al . Metabolic flexibility as an adaptation to energy resources and requirements in health and disease [J]. Endocr Rev , 2018 , 39 ( 4 ): 489 - 517 .
TAN Y , ZHANG Z , ZHENG C , et al . Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: Preclinical and clinical evidence [J]. Nat Rev Cardiol , 2020 , 17 ( 9 ): 585 - 607 .
BERTRAND L , HORMAN S , BEAULOYE C , et al . Insulin signalling in the heart [J]. Cardiovasc Res , 2008 , 79 ( 2 ): 238 - 248 .
HEATHER L C , CLARKE K. Metabolism , hypoxia and the diabetic heart [J]. J Mol Cell Cardiol , 2011 , 50 ( 4 ): 598 - 605 .
LOPASCHUK G D , USSHER J R , FOLMES C D , et al . Myocardial fatty acid metabolism in health and disease [J]. Physiol Rev , 2010 , 90 ( 1 ): 207 - 258 .
BIRKENFELD A L , JORDAN J , DWORAK M , et al . Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts [J]. Pharmacol Ther , 2019 , doi: 10.1016/j.pharmthera.2018.08.015 http://dx.doi.org/10.1016/j.pharmthera.2018.08.015 .
ZAMORA M , VILLENA J A . Contribution of impaired insulin signaling to the pathogenesis of diabetic cardiomyopathy [J]. Int J Mol Sci , 2019 , 20 ( 11 ): 2833 .
PALOMER X , SALVADO L , BARROSO E , et al . An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy [J]. Int J Cardiol , 2013 , 168 ( 4 ): 3160 - 3172 .
COORT S L M , BONEN A , VAN DER VUSSE G J , et al . Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: Role of sarcolemmal substrate transporters [J]. Mol Cell Biochem , 2007 , 299 ( 1/2 ): 5 - 18 .
LOPASCHUK G D . Metabolic abnormalities in the diabetic heart [J]. Heart Fail Rev , 2002 , 7 ( 2 ): 149 - 159 .
GRIFFIN T M , HUMPHRIES K M , KINTER M , et al . Nutrient sensing and utilization: Getting to the heart of metabolic flexibility [J]. Biochimie , 2016 , doi: 10.1016/j.biochi.2015.10.013 http://dx.doi.org/10.1016/j.biochi.2015.10.013 .
LEHRKE M , MARX N . Diabetes mellitus and heart failure [J]. Am J Med , 2017 , 130 ( 6S ): S40 - S50 .
SAOTOME M , IKOMA T , HASAN P , et al . Cardiac insulin resistance in heart failure: The role of mitochondrial dynamics [J]. Int J Mol Sci , 2019 , 20 ( 14 ): 3552 .
DESEROIS M , SIDELL R J , GAUGUIER D , et al . Initial steps of insulin signaling and glucose transport are defective in the type 2 diabetic rat heart [J]. Cardiovasc Res , 2004 , 61 ( 2 ): 288 - 296 .
AMARAL N , OKONKO D O . Metabolic abnormalities of the heart in type Ⅱ diabetes [J]. Diabetes Vasc Dis Re , 2015 , 12 ( 4 ): 239 - 248 .
BHATT K N , BUTLER J . Myocardial energetics and heart failure: A review of recent therapeutic trials [J]. Curr Heart Fail Rep , 2018 , 15 ( 3 ): 191 - 197 .
LORENZO O , PICATOSTE B , ARES-CARRASCO S , et al . Potential role of nuclear factor kappaB in diabetic cardiomyopathy [J]. Mediators Inflamm , 2011 , doi: 10.1155/2011/652097 http://dx.doi.org/10.1155/2011/652097 .
CIVIDINI F , SCOTT B T , SUAREZ J , et al . Ncor2/PPAR α -dependent upregulation of MCUb in the type 2 diabetic heart impacts cardiac metabolic flexibility and function [J]. Diabetes , 2021 , 70 ( 3 ): 665 - 679 .
BELKE D D , LARSEN T S , GIBBS E M , et al . Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice [J]. Am J Physiol Endocrinol Metab , 2000 , 279 ( 5 ): 1104 - 1113 .
ABDURRACHIM D , NABBEN M , HOEER V , et al . Diabetic db/ db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations [J]. Cardiovasc Res , 2017 , 113 ( 10 ): 1148 - 1160 .
HERRERO P , PETERSON L R , MCGILL J B , et al . Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus [J]. J Am Coll Cardiol , 2006 , 47 ( 3 ): 598 - 604 .
PETERSON L R , HERRERO P , MCGILL J , et al . Fatty acids and insulin modulate myocardial substrate metabolism in humans with type 1 diabetes [J]. Diabetes , 2008 , 57 ( 1 ): 32 - 40 .
SEFEROVIC P M , PAULUS W J . Clinical diabetic cardiomyopathy: A two-faced disease with restrictive and dilated phenotypes [J]. Eur Heart J , 2015 , 36 ( 27 ): 1718 - 1727 , 1727a-1727c.
TENENBAUM A , FISMAN E Z , SCHWAMMENTHAL E , et al . Increased prevalence of left ventricular hypertrophy in hypertensive women with type 2 diabetes mellitus [J]. Cardiovasc Diabetol , 2003 , doi: 10.1186/1475-2840-2-14 http://dx.doi.org/10.1186/1475-2840-2-14 .
WENDE A R , KIM J , HOLLAND W L , et al . Glucose transporter 4-deficient hearts develop maladaptive hypertrophy in response to physiological or pathological stresses [J]. Am J Physiol Heart Circ Physiol , 2017 , 313 ( 6 ): H1098 - H1108 .
LE PAGE L M , RIDER O J , LEWIS A J , et al . Increasing pyruvate dehydrogenase flux as a treatment for diabetic cardiomyopathy: A combined 13C hyperpolarized magnetic resonance and echocardiography study [J]. Diabetes , 2015 , 64 ( 8 ): 2735 - 2743 .
CHONG C R , CLARKE K , LEVELT E . Metabolic remodeling in diabetic cardiomyopathy [J]. Cardiovasc Res , 2017 , 113 ( 4 ): 422 - 430 .
JIA G , HILL M A , SOWERS J R . Diabetic cardiomyopathy: An update of mechanisms contributing to this clinical entity [J]. Circ Res , 2018 , 122 ( 4 ): 624 - 638 .
RITCHIE R H , ABEL E D . Basic mechanisms of diabetic heart disease [J]. Circ Res , 2020 , 126 ( 11 ): 1501 - 1525 .
PETERSON L R , GROPLER R J . Metabolic and molecular imaging of the diabetic cardiomyopathy [J]. Circ Res , 2020 , 126 ( 11 ): 1628 - 1645 .
KARWI Q G , UDDIN G M , HO K L , et al . Loss of metabolic flexibility in the failing heart [J]. Front Cardiovasc Med , 2018 , 6 ( 5 ): 68 .
NIRENGI S , SILVA C P V D , STANFORD K I . Disruption of energy utilization in diabetic cardiomyopathy: A mini review [J]. Curr Opin Pharmacol , 2020 , doi: 10.1016/j.coph.2020.08.015 http://dx.doi.org/10.1016/j.coph.2020.08.015 .
NISHIKAWA T , EDELSTEIN D , DU X L , et al . Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage [J]. Nature , 2000 , 404 ( 6779 ): 787 - 790 .
RIEHLE C , ABEL E D . Insulin signaling and heart failure [J]. Circ Res . 2016 , 118 ( 7 ): 1151 - 1169 .
RITTE DOENST T , NGUYEN T D , ABEL E D . Cardiac metabolism in heart failure: Implications beyond ATP production [J]. Circ Res , 2013 , 113 ( 6 ): 709 - 724 .
LORENZO-ALMOROS A , CEPEDA-RODRIGO J M , LORENZO Ó . Diabetic cardiomyopathy [J]. Rev Clin Esp (Barc) , 2022 , 222 ( 2 ): 100 - 111 .
薛建军 , 范强 , 杨丽霞 , 等 . 糖尿病心肌病发病机制及中医药治疗概述 [J]. 中国实验方剂学杂志 , 2017 , 23 ( 22 ): 211 - 217 .
KAUR R , KAUR M , SINGH J . Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: Molecular insights and therapeutic strategies [J]. Cardiovasc Diabetol , 2018 , 17 ( 1 ): 121 .
TAREEN S H K , KUTMON M , ADRIAENS M E , et al . Exploring the cellular network of metabolic flexibility in the adipose tissue [J]. Genes Nutr , 2018 , 5 ( 13 ): 17 .
KALRA S , UNNIKRISHNAN A G , BARUAH M P , et al . Metabolic and energy imbalance in dysglycemia-based chronic disease [J]. Diabetes Metab Syndr Obes , 2021 , 15 ( 14 ): 165 - 184 .
刘艳丽 , 王秀秀 , 韩金祥 . 中医“气”学说研究60年 [J]. 辽宁中医杂志 , 2014 , 41 ( 11 ): 2299 - 2303 .
张永忠 . 论中医学人体之气的实质是新陈代谢 [J]. 中国中医基础医学杂志 , 2000 , 6 ( 5 ): 8 - 11 .
韩晶岩 . 心气虚血瘀的科学内涵和芪参益气滴丸补气活血的作用机理 [J]. 世界科学技术—中医药现代化 , 2019 , 21 ( 2 ): 139 - 147 .
DUNCAN J G , FINCK B N . The PPARalpha-PGC-1alpha axis controls cardiac energy metabolism in healthy and diseased myocardium [J]. PPAR Res , 2008 , doi: 10.1155/2008/253817 http://dx.doi.org/10.1155/2008/253817 .
许德 , 杨洪娟 , 张娟 . 从“瘀”论治糖尿病性心肌病 [J]. 陕西中医学院学报 , 2013 , 36 ( 2 ): 7 - 8 .
张惜燕 , 胡勇 , 邢玉瑞 . 糖尿病现代中医创新病机辨析 [J]. 世界中医药 , 2022 , 17 ( 4 ): 512 - 515 .
张米鎿 , 寇兰俊 , 李淑艳 , 等 . 气血理论在心系疾病中的应用 [J]. 现代中医临床 , 2021 , 28 ( 1 ): 64 - 68 .
于晓原 , 王艳丽 , 孙烨 , 等 . 参芪血府逐瘀汤对糖尿病心肌病的临床作用及机制 [J]. 心脏杂志 , 2021 , 31 ( 6 ): 619 - 623 .
陈志阳 , 林晓阳 , 金莹 , 等 . 黄芪保心汤对糖尿病心肌病心功能不全患者心肌重塑的影响及作用机制研究 [J]. 浙江中医杂志 , 2020 , 55 ( 1 ): 6 - 8 .
常晓 , 李惠林 , 王玲 , 等 . 益气活血方治疗糖尿病心肌病合并心力衰竭的临床观察 [J]. 中医药通报 , 2015 , 14 ( 3 ): 53 - 55 .
曹长峰 . 益心煎剂治疗糖尿病心肌病的临床研究 [J]. 中国现代医生 , 2015 , 53 ( 1 ): 64 - 66 .
董又滋 , 赵泉霖 , 高丽君 . 黄芪-当归药对治疗糖尿病心肌病的分子机制 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 18 ): 16 - 24 .
RHOFF J , TIAN R . Metabolism in cardiomyopathy: Every substrate matters [J]. Cardiovasc Res , 2017 , 113 ( 4 ): 411 - 421 .
成文堃 , 赵明镜 , 王蕾 , 等 . 心力衰竭底物代谢重构模式及其机制的研究进展 [J]. 中国实验方剂学杂志 , 2020 , 26 ( 5 ): 210 - 219 .
王丽君 . 糖尿病性心肌病的中西医研究概况 [J]. 甘肃医药 , 2021 , 40 ( 6 ): 486 - 489 .
于永慧 , 张佩 , 刘剑刚 , 等 . 气血并治方有效组分干预H/R损伤心肌细胞AMPK相关糖脂代谢通路的分析 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 6 ) : 89 - 95 .
王臻 , 李洁白 , 董昕 , 等 . 补阳还五汤对舒张性心衰大鼠心肌线粒体能量代谢及 AMPK/PPARα信号通路的影响 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 9 ) : 12 - 17 .
PALM W , THOMPSON C B . Nutrient acquisition strategies of mammalian cells [J]. Nature , 2017 , 546 ( 7657 ): 234 - 242 .
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