摘要
心力衰竭后心肌底物代谢严重受损,对葡萄糖和脂肪酸等底物的选择和利用发生重构,心肌产能不足,可导致心功能障碍和进展性左心室重构。传统观念认为,心衰时心脏从脂肪酸代谢向葡萄糖代谢转化,但近年来有些研究结果与此观点相矛盾,关于心衰后心肌能量底物代谢的改变及其调控机制的研究结论尚未统一,心衰的代谢治疗发展缓慢,因此,探讨导致这些结论异质性的原因对明确心衰底物代谢模式和研发代谢靶向药物十分必要。该综述总结了正常心肌在生理条件下的代谢模式及调控机制,同时,从心衰的病因、严重程度、持续时间、研究的物种、动物模型和代谢检测方法等多个角度,重点阐述和比较了由缺血性心脏病、压力负荷、容量负荷及扩张型心肌病诱导的心衰中心脏底物代谢的异常,初步分析了不同研究中相关结论的一致性和差异性,并对代谢治疗的未来趋势展开论述,以期初步总结出心衰后葡萄糖代谢和脂肪酸代谢变化的规律及其分子机制,并为代谢靶向治疗的研究提供线索。
Myocardial substrate metabolism is severely impaired after heart failure,and the selection and utilization of substrates,such as glucose and fatty acids,are remodeled,resulting in insufficient myocardial productivity,cardiac dysfunction and progressive left ventricular remodeling.It is believed traditionally that the heart changes from fatty acid metabolism to glucose metabolism during heart failure,which however is contradictory with some findings in recent years.No consistent conclusion can be drawn from studies on the changes of myocardial energy substrate metabolism and its regulatory mechanism after heart failure.Metabolic treatment for heart failure has developed slowly.Therefore,it is necessary to explore the reasons for heterogeneity of these conclusions for defining the metabolic patterns of heart failure substrates and developing metabolically targeted drugs.This review summarizes the metabolic patterns and regulatory mechanisms of normal myocardium under physiological conditions,focuses on the elaboration and comparison of myocardial substrates metabolic abnormalities in heart failure induced by ischemic heart disease,pressure load,volume load and dilated cardiomyopathy in such aspects as etiology,severity,duration of heart failure,species studied,animal models and metabolic detection methods,and makes a preliminary analysis on the consistency and differences of relevant conclusions in various studies,and discusses the future trend of metabolic treatment,with the aim to summarize the rules and molecular mechanism of glucose metabolism and fatty acid metabolism after heart failure and provide clues for the research of metabolic targeted therapy.
作者
成文堃
赵明镜
王蕾
陆梓雯
杨涛
杨京京
李彤
王保福
李洋
CHENG Wen-kun;ZHAO Ming-jing;WANG Lei;LU Zi-wen;YANG Tao;YANG Jing-jing;LI Tong;WANG Bao-fu;LI Yang(Key Laboratory of Internal Medicine of Traditional Chinese Medicine Under Ministry of Education and Dongzhimen Hospital,Integrated Traditional Chinese and Western Medicine and Blood Research Laboratory,Beijing University of Chinese Medicine,Beijing 100700,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第5期210-219,共10页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81541075)
北京市自然科学基金重点项目(7161008).
关键词
心力衰竭
代谢重构
脂肪酸代谢
葡萄糖代谢
代谢灵活性
heart failure
metabolic remodeling
fatty acid metabolism
glucose metabolism
metabolic flexibility
