Wang Mengyuan, Chen Jinhong, Zhang Zhongzheng, Wang Tianyu, Zhao Jiaqi, Wang Xiao, Wang Junyan, Zhuang Haowen
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Nutrients. 2025 Aug 28;17(17):2800. doi: 10.3390/nu17172800.
Post-myocardial infarction (MI) heart failure (HF) is characterized by myocardial energy metabolism disorder, with excessive glycolysis playing a key role in its progression. Silybin (SIL), a flavonoid derived from Silybum marianum, has demonstrated hepatoprotective and metabolic regulatory effects. However, the role of this flavonoid in ameliorating post-myocardial infarction heart failure (post-MI HF) by modulating energy metabolism remains unclear.
This study employed an oxygen-glucose deprivation (OGD) model to induce myocardial cell injury in vitro, with YC-1 treatment used to inhibit hypoxia-inducible factor-1α (HIF-1α) for mechanistic validation. A myocardial infarction-induced HF mouse model was used for in vivo experiments.
In vitro, SIL enhanced cell viability, increased ATP levels, and decreased lactate production and reactive oxygen species (ROS) accumulation in OGD-treated myocardial cells. SIL downregulated the mRNA and protein expression of HIF-1α, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA) while inhibiting HIF-1α nuclear translocation. Furthermore, SIL suppressed glycolytic proteins (PFKFB3, GLUT1, and LDHA) in a manner comparable to the HIF-1α inhibitor YC-1. This confirms that SIL's inhibition of glycolysis is HIF-1α-dependent. In vivo, SIL treatment improved cardiac function parameters (LVEF and LVFS) and attenuated left ventricular remodeling (LVID;d and LVID;s) in post-MI HF mice. Additionally, myocardial fibrosis markers were significantly reduced, accompanied by a decrease in the myocardial mRNA and protein expression of glycolytic proteins, including HIF-1α, PFKFB3, GLUT1, and LDHA.
Silybin effectively ameliorates post-myocardial infarction heart failure through the HIF-1α-mediated regulation of glycolysis, leading to improved myocardial energy metabolism and enhanced cardiac function.
心肌梗死后心力衰竭以心肌能量代谢紊乱为特征，糖酵解过度在其进展中起关键作用。水飞蓟宾（SIL）是一种从水飞蓟中提取的黄酮类化合物，已显示出肝脏保护和代谢调节作用。然而，这种黄酮类化合物通过调节能量代谢改善心肌梗死后心力衰竭（心肌梗死后HF）的作用仍不清楚。
本研究采用氧糖剥夺（OGD）模型在体外诱导心肌细胞损伤，并用YC-1处理抑制缺氧诱导因子-1α（HIF-1α）进行机制验证。使用心肌梗死诱导的HF小鼠模型进行体内实验。
在体外，SIL增强了OGD处理的心肌细胞的活力，增加了ATP水平，降低了乳酸生成和活性氧（ROS）积累。SIL下调了HIF-1α、6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3（PFKFB3）、葡萄糖转运蛋白1（GLUT1）和乳酸脱氢酶A（LDHA）的mRNA和蛋白表达，同时抑制HIF-1α核转位。此外，SIL以与HIF-1α抑制剂YC-1相当的方式抑制糖酵解蛋白（PFKFB3、GLUT1和LDHA）。这证实了SIL对糖酵解的抑制是HIF-1α依赖性的。在体内，SIL治疗改善了心肌梗死后HF小鼠的心脏功能参数（左心室射血分数和左心室短轴缩短率），并减轻了左心室重构（左心室内径舒张末期和左心室内径收缩末期）。此外，心肌纤维化标志物显著降低，同时心肌中包括HIF-1α、PFKFB3、GLUT1和LDHA在内的糖酵解蛋白的mRNA和蛋白表达也减少。
水飞蓟宾通过HIF-1α介导的糖酵解调节有效改善心肌梗死后心力衰竭，从而改善心肌能量代谢并增强心脏功能。
