Kirenol Ameliorates Myocardial Ischemia-Reperfusion Injury by Promoting Mitochondrial Function and Inhibiting Inflammasome Activation.

IF 3.1 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiovascular Drugs and Therapy Pub Date : 2024-11-12 DOI:10.1007/s10557-024-07635-4
Lei Pan, Mingqiang Fu, Xiang-Lin Tang, Yunlong Ling, Yangang Su, Junbo Ge
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Abstract

Purpose: Macrophage-mediated inflammation plays a crucial role in the pathophysiological process of myocardial ischemia/reperfusion (I/R) injury. Recent studies have highlighted the importance of mitochondrial function and inflammasome activation in the inflammatory process. Kirenol, a well-known natural compound, has been shown to regulate inflammation in various diseases. This study investigated whether Kirenol could exert anti-inflammatory effects on macrophages during myocardial I/R injury.

Methods: Mouse myocardial I/R models were established by 45 min of ischemia followed by 24 h of reperfusion. Saline or Kirenol treatment was administered. In vivo assessments included the evaluation of cardiac function, infarcted area, and immune cell infiltration. Subsequently, bone marrow-derived macrophages (BMDMs) were isolated, and mitochondrial function and pyroptosis were assessed. Furthermore, the study compared the cardioprotective effects of Kirenol with a specific NOX1/NOX4 inhibitor, GKT137831.

Results: Kirenol gavage improved cardiac function, decreased infarct area, and alleviated inflammatory infiltration in mice subjected to myocardial I/R injury. Mechanistically, Kirenol inhibited NOX1 and NOX4 and enhanced mitochondrial function, ultimately attenuating the pyroptosis of macrophages. The therapeutic effects of Kirenol and GKT137831 were not significantly different.

Conclusion: This study demonstrates that Kirenol mitigates myocardial I/R injury by inhibiting NOX1 and NOX4, restoring mitochondrial function, and ameliorating macrophage pyroptosis.

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Kirenol 通过促进线粒体功能和抑制炎症小体激活改善心肌缺血再灌注损伤
目的:巨噬细胞介导的炎症在心肌缺血/再灌注(I/R)损伤的病理生理过程中起着至关重要的作用。最近的研究强调了线粒体功能和炎性体激活在炎症过程中的重要性。Kirenol 是一种著名的天然化合物,已被证明能调节各种疾病的炎症反应。本研究探讨了 Kirenol 是否能在心肌 I/R 损伤过程中对巨噬细胞产生抗炎作用:方法:小鼠心肌 I/R 模型通过 45 分钟缺血和 24 小时再灌注建立。小鼠接受生理盐水或 Kirenol 治疗。体内评估包括心功能、梗死面积和免疫细胞浸润评估。随后,分离了骨髓源性巨噬细胞(BMDMs),并评估了线粒体功能和脓毒症。此外,该研究还比较了基瑞诺与特异性 NOX1/NOX4 抑制剂 GKT137831 的心脏保护作用:结果:灌胃 Kirenol 可改善心肌 I/R 损伤小鼠的心功能、减少梗死面积并减轻炎症浸润。从机理上讲,Kirenol能抑制NOX1和NOX4并增强线粒体功能,最终减轻巨噬细胞的脓毒症。Kirenol 和 GKT137831 的治疗效果没有显著差异:本研究表明,喹诺酮可通过抑制 NOX1 和 NOX4、恢复线粒体功能和改善巨噬细胞的脓毒症减轻心肌 I/R 损伤。
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来源期刊
Cardiovascular Drugs and Therapy
Cardiovascular Drugs and Therapy 医学-心血管系统
CiteScore
8.30
自引率
0.00%
发文量
110
审稿时长
4.5 months
期刊介绍: Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.
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