心力衰竭中心脏能量代谢变化研究进展

doi:10.12114/j.issn.1007-9572.2024.0654

摘要/Abstract

摘要： 射血分数保留型心力衰竭（HFpEF）是指左心室射血分数≥50%但存在心力衰竭的症状和临床体征的临床综合征，目前临床上约有50%的心力衰竭患者为HFpEF。越来越多的证据表明心力衰竭是一种代谢性疾病，其能量代谢变化显著，而能量代谢网络尚未明晰。本综述将从糖代谢、脂代谢、酮体代谢及氨基酸代谢4个方面阐述心力衰竭中能量代谢的变化，通过HFpEF与射血分数下降型心力衰竭（HFrEF）的对比研究进一步了解不同代谢在HFpEF心脏中能量代谢的变化和意义，明确心力衰竭与各底物能量代谢之间的关系，从心脏能量代谢角度为不同类型心力衰竭的精准治疗提供理论依据和新的治疗观念。

关键词: 心力衰竭, 射血分数保留型心力衰竭, 射血分数降低型心力衰竭, 能量代谢, 葡萄糖代谢, 脂肪酸代谢, 酮体代谢, 氨基酸代谢

Abstract:

Heart failure with preserved ejection fraction (HFpEF) refers to a clinical syndrome characterized by a left ventricular ejection fraction of ≥50% and the presence of symptoms and clinical signs of heart failure. Currently, approximately 50% of patients with heart failure in clinical practice have heart failure with preserved ejection fraction. An increasing body of evidence suggests that heart failure is a metabolic disease with significant changes in energy metabolism, and the complex energy metabolic network is not yet fully understood. This review will discuss the changes in energy metabolism in heart failure from four aspects: glucose metabolism, lipid metabolism, ketone body metabolism, and amino acid metabolism. By comparing HFpEF with heart failure with reduced ejection fraction (HFrEF), the study further demonstrates the changes and significance of different metabolisms in the energy metabolism of the heart with HFpEF, clarifies the relationship between heart failure and energy metabolism, and provides theoretical bases and new treatment concepts for the precise treatment of different types of heart failure from a metabolic perspective.

Key words: Heart failure, Heart failure with preserved ejection fraction, Heart failure with reduced ejection fraction, Energy metabolism, Glucose metabolism, Fatty acid metabolism, Ketone body metabolism, Amino acid metabolism

马双双,邢岩江,张佳玮,等. 心力衰竭中心脏能量代谢变化研究进展[J]. 中国全科医学, 2025, 28(30): 3831-3840. DOI: 10.12114/j.issn.1007-9572.2024.0654.
MA Shuangshuang,XING Yanjiang,ZHANG Jiawei, et al. Research Progress on Cardiac Energy Metabolic Changes in Heart Failure with Preserved Ejection Fraction[J]. Chinese General Practice, 2025, 28(30): 3831-3840. DOI: 10.12114/j.issn.1007-9572.2024.0654.

图/表 4

图1 正常心脏葡萄糖、脂肪酸、酮体和氨基酸代谢及其代谢酶注：葡萄糖通过葡萄糖转运蛋白1/4（GLUT1/4）转运到细胞中，然后进行糖酵解产生丙酮酸，通过线粒体丙酮酸载体（MPC）转运到线粒体中，并通过丙酮酸脱氢酶（PDH）转化为乙酰辅酶A进入三羧酸循环或转化为乳酸，然后通过乳酸脱氢酶4（MCT4）被其运出细胞；脂肪酸部分通过脂肪酸转运蛋白（CD36/FATP-1）转运到心肌细胞中被酯化为脂肪酰辅酶A（Fatty acyl CoA），游离FA可以过氧化物酶体增殖物激活受体（PPARs），Fatty acyl CoA酰基通过肉碱棕榈酰转移酶（CPT）-1转移到肉碱上并转运到线粒体中，CPT-2将其转化回脂肪酰基辅酶A，然后通过β氧化产生乙酰辅酶A；酮体β-羟基丁酸酯（β-OHB）通过单羧酸转运蛋白1（SLC16A1）运输到细胞中，通过β-羟基丁酸脱氢酶1（BDH1）催化氧化为乙酰乙酸酯。然后通过琥珀酰辅酶A（SCOT）激活产生乙酰辅酶A；支链氨基酸（BCAA）通过LIVCS转运到细胞中，BCAA在线粒体中被线粒体支链转氨酶（BCATm）转化为酮酸，通过BCKDH形成乙酰辅酶A和琥珀酰辅酶A。脂肪酸β氧化、葡萄糖氧化、酮氧化和支链氨基酸氧化生成的乙酰辅酶A进入TCA循环，生成黄素腺嘌呤二核苷酸（FADH2）和烟酰胺腺嘌呤二核苷酸（NADH）进入电子传递链，消耗氧气生成三磷酸腺苷（ATP）。

Figure 1 Glucose，fatty acids，ketone bodies and amino acid metabolism and their metabolic enzymes in the normal heart

图2 衰竭心脏葡萄糖、脂肪酸、酮体和氨基酸代谢变化及潜在靶点治疗注：丙酮酸脱氢酶（PDH）激酶（PDK）抑制剂减轻PDK对PDH的抑制作用刺激葡萄糖氧化；MCT4抑制剂通过抑制乳酸外排缓解心脏肥大和心脏衰竭；CPT-1抑制剂降低CPT-1对脂肪酸摄取到线粒体中的作用；PPARα激动剂通过增加脂肪酸在心外组织中的利用率减少心肌中脂肪酸供应；β-OHB输注用过增加循环酮水平促进心脏进一步摄取和氧化；钠-葡萄糖协同转运蛋白2型（SGLT2）抑制剂模拟空腹状态导致内源性酮体水平升高；支链酮酸脱氢酶激酶（BCKDK）抑制剂减轻BCKDK的抑制作用，从而刺激BCKDH的作用并诱导BCAA氧化的通量；红色箭头表示在射血分数保留型心力衰竭中的变化，蓝色箭头表示在射血分数下降型心力衰竭中的变化，黄色箭头表示在两者中均变化；朝上的箭头表示增加，向下的箭头表示减少。

Figure 2 Changes in glucose，fatty acid，ketone bodies and amino acid metabolism in the failing heart and potential targets for therapy

表1 心肌能量代谢的改变

Table 1 Alterations in myocardial energy metabolism in heart failure

能量代谢途径	能量代谢
能量代谢途径	健康心脏	HFrEF	HFpEF
糖酵解	2%~8%	+	+
葡萄糖氧化	20%~40%	-	-
脂肪酸氧化	40%~60%	+/-	+
酮体氧化	10%~15%	+	-
氨基酸氧化	1%~2%	-	-

表2 心脏代谢调节药物作用机制及研究进展

Table 2 Mechanisms of action of cardiac metabolism regulating drugs and research progress

心脏代谢调节药物	能量代谢途径	作用机制	研究进展
曲美他嗪	脂肪酸氧化（-）、葡萄糖氧化（+）	抑制脂肪酸氧化，增加AMPK信号传导	缓解HF，可作为常规HF治疗的附加治疗
哌克昔林依托莫昔	脂肪酸氧化（-）	CPT-1抑制剂	缓解HFrEF、抗心绞痛（具肝毒性及神经毒性）
PPARα激活剂	脂肪酸氧化（+）、葡萄糖代谢（+）	上调CPT-1、激活GLUT4	心肌缺血再灌注损伤、HF的临床前研究
二氯乙酸盐	葡萄糖氧化（+）	抑制PDK并激活PDH，减少心肌耗氧量	临床试验阶段，缓解HFrEF与HFpEF
辅酶Q10	线粒体电子传递链（+）	增强心肌ATP生成改善心肌能量状态	HF辅助治疗
依拉米肽	线粒体电子传递链（+）	稳定线粒体膜	临床试验阶段，缓解HFrEF
直接输注酮体生酮饮食	酮体氧化（+）	增加心肌酮体氧化	临床前研究
SGLT2i	酮体氧化（+）	增加心肌酮体氧化	2型糖尿病合并HF
β-受体阻滞剂	脂肪酸氧化（-）	通过降低心率和心肌收缩力减少心肌能量消耗	HFrEF核心治疗药物
基因治疗	线粒体功能（+）	增强线粒体ATP转运和激活线粒体生物发生，从而改善心肌能量供应	临床前研究
干细胞治疗	线粒体功能（+）	增强心肌细胞恢复，修复心肌功能	临床前研究

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