Hypericin attenuates myocardial ischemia-reperfusion injury by enhancing mitochondrial energy metabolism via AMPK/PGC-1α signaling pathway

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-15 DOI:10.1016/j.tice.2025.103088

LI Huihui , BAO Yali , LI Wanyue , XIN Huitian , GAO Xiaofeng , Dina AINIWAR , LING Can , Gulinigaer ANWAIER , SUN Zhan

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引用次数: 0

Abstract

Background

Although blood flow is restored following the treatment of acute myocardial infarction (AMI), myocardial Ischaemia /reperfusion can still cause cardiac damage, potentially leading to cardiac decompensation and, ultimately, heart failure. This study aimed to investigate the effects of Hypericin (Hyp) on the hearts of rats with myocardial ischaemia-reperfusion injury (MIRI) and its underlying mechanisms.

Methods

Male Sprague-Dawley rats and H9C2 cells underwent MIRI and hypoxia/reoxygenation (H/R) modelling after Hyp administration to assess the compound's effects on cardiac and cardiomyocyte characteristics, as well as mitochondrial energy metabolism. A range of techniques, including 2,3,5-triphenyltetrazolium chloride staining, haematoxylin-eosin staining, echocardiography, enzyme-linked immunosorbent assay, quantitative proteomics analysis, molecular docking, and Western blotting were employed to further characterize Hyp's cardioprotective effects and its influence on related molecular expressions. TUNEL staining and Western blotting were also used to examine the morphological, molecular, and functional phenotypes of H/R-treated cardiomyocytes.

Results

Hyp significantly reduced myocardial infarct size and improved cardiac function in MIRI rats. Hyp increased cardiomyocyte viability while decreasing cardiomyocyte damage. The cardioprotective effects of Hyp were primarily mediated by alleviating mitochondrial dysfunction and oxidative stress, mainly through the adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator 1-alpha (PGC-1α) signalling pathway.

Conclusion

Hyp regulates the AMPK/PGC-1α signalling pathway to improve mitochondrial energy metabolism and reduce oxidative stress, thereby mitigating MIRI in rats.

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金丝桃素通过AMPK/PGC-1α信号通路增强线粒体能量代谢，减轻心肌缺血再灌注损伤

背景：虽然急性心肌梗死（AMI）治疗后血流量恢复，但心肌缺血/再灌注仍可引起心脏损伤，可能导致心脏失代偿，最终导致心力衰竭。本研究旨在探讨金丝桃素（Hyp）对心肌缺血再灌注损伤（MIRI）大鼠心脏的影响及其机制。方法对Sprague-Dawley大鼠和H9C2细胞进行MIRI和缺氧/再氧化（H/R）模型，以评估Hyp给药后化合物对心脏和心肌细胞特征以及线粒体能量代谢的影响。采用2,3,5-三苯四唑氯染色、血红素-伊红染色、超声心动图、酶联免疫吸附测定、定量蛋白质组学分析、分子连接和Western blotting等一系列技术进一步表征Hyp的心脏保护作用及其对相关分子表达的影响。TUNEL染色和Western blotting检测H/ r处理心肌细胞的形态学、分子和功能表型。结果shyp可明显减少心肌梗死面积，改善心功能。Hyp增加心肌细胞活力，减少心肌细胞损伤。Hyp的心脏保护作用主要是通过减轻线粒体功能障碍和氧化应激介导的，主要是通过腺苷单磷酸活化蛋白激酶(AMPK)/过氧化物酶体增殖体活化受体γ共激活因子1- α (PGC-1α)信号通路。结论hyp通过调节AMPK/PGC-1α信号通路，改善线粒体能量代谢，减轻氧化应激，从而减轻大鼠MIRI。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.