Bardoxolone Methyl Ameliorates Myocardial Ischemia/Reperfusion Injury by Activating the Nrf2/HO-1 Signaling Pathway.

IF 3.4 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiovascular Therapeutics Pub Date : 2023-02-22 eCollection Date: 2023-01-01 DOI:10.1155/2023/5693732

Anwu Huang, Zhaolin Wang, Hua Tang, Zhuyin Jia, Xiaojun Ji, Xuehua Yang, Wenbing Jiang

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Abstract

Background: Myocardial ischemia/reperfusion (I/R) injury is a severe heart problem resulting from restoring coronary blood flow to the myocardium after ischemia. This study is aimed at ascertaining the therapeutic efficiency and action mechanism of bardoxolone methyl (BARD) in myocardial I/R injury.

Methods: In male rats, myocardial ischemia was performed for 0.5 h, and then, reperfusion lasted for 24 h. BARD was administrated in the treatment group. The animal's cardiac function was measured. Myocardial I/R injury serum markers were detected via ELISA. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to estimate the infarction. H&E staining was used to evaluate the cardiomyocyte damage, and Masson trichrome staining was used to observe the proliferation of collagen fiber. The apoptotic level was assessed via the caspase-3 immunochemistry and TUNEL staining. Oxidative stress was measured through malondialdehyde, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, and inducible nitric oxide synthases. The alteration of the Nrf2/HO-1 pathway was confirmed via western blot, immunochemistry, and PCR analysis.

Results: The protective effect of BARD on myocardial I/R injury was observed. In detail, BARD decreased cardiac injuries, reduced cardiomyocyte apoptosis, and inhibited oxidative stress. For mechanisms, BARD treatment significantly activates the Nrf2/HO-1 pathway.

Conclusion: BARD ameliorates myocardial I/R injury by inhibiting oxidative stress and cardiomyocyte apoptosis via activating the Nrf2/HO-1 pathway.

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Bardoxolone Methyl 通过激活 Nrf2/HO-1 信号通路改善心肌缺血再灌注损伤

背景：心肌缺血/再灌注（I/R）损伤是心肌缺血后恢复冠状动脉血流所导致的严重心脏问题。本研究旨在确定甲基巴尔多酚酮（BARD）对心肌缺血再灌注损伤的治疗效果和作用机制：方法：雄性大鼠心肌缺血 0.5 h，再灌注 24 h。测量动物的心功能。通过 ELISA 检测心肌 I/R 损伤血清标志物。2,3,5-三苯基氯化四氮唑（TTC）染色用于评估心肌梗死。H&E 染色用于评估心肌细胞损伤，Masson 三色染色用于观察胶原纤维的增殖。通过 Caspase-3 免疫化学和 TUNEL 染色评估细胞凋亡水平。通过丙二醛、8-羟基-2'-脱氧鸟苷、超氧化物歧化酶和诱导型一氧化氮合酶测量氧化应激。通过 Western 印迹、免疫化学和 PCR 分析证实了 Nrf2/HO-1 通路的改变：结果：观察到 BARD 对心肌 I/R 损伤有保护作用。具体而言，BARD可减少心脏损伤、减少心肌细胞凋亡并抑制氧化应激。在机制上，BARD能明显激活Nrf2/HO-1通路：结论：BARD 通过激活 Nrf2/HO-1 通路抑制氧化应激和心肌细胞凋亡，从而改善心肌 I/R 损伤。

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来源期刊

Cardiovascular Therapeutics 医学-心血管系统

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged. Subject areas include (but are by no means limited to): Acute coronary syndrome Arrhythmias Atherosclerosis Basic cardiac electrophysiology Cardiac catheterization Cardiac remodeling Coagulation and thrombosis Diabetic cardiovascular disease Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF) Hyperlipidemia Hypertension Ischemic heart disease Vascular biology Ventricular assist devices Molecular cardio-biology Myocardial regeneration Lipoprotein metabolism Radial artery access Percutaneous coronary intervention Transcatheter aortic and mitral valve replacement.