Delphinidin inhibits the ALOX15-mediated ferroptosis in rats to alleviate myocardial ischemia and reperfusion injury

IF 3.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular cell research Pub Date : 2025-06-11 DOI:10.1016/j.bbamcr.2025.120006

Qing Sun , Mei Lv , Zhen Wang

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引用次数: 0

Abstract

Objective

The present study aimed to investigate the role of delphinidin (Dp) in myocardial ischemia-reperfusion injury (MIRI) and elucidate the underlying mechanism.

Methods

MIRI animal models were established in Sprague-Dawley rats by ligation of left anterior descending coronary artery (LAD) ligation for 30 min and reperfusion of 2 h. Primary cardiomyocytes and H9C2 cells were stimulated by oxygen-glucose deprivation/regain (OGD/R) conditions for mimicking MIRI cell models. Ultrasound, hematoxylin and eosin and Masson staining were used to evaluate cardiac function and myocardial infarction in rats following Dp treatment. Cell counting kit-8 assay and flow cytometry were performed to detect cell viability and apoptosis, respectively. Western blotting and quantitative real-time polymerase chain reaction measured ALOX15 expression. Additionally, ferroptosis-related factors and lactate dehydrogenase levels were detected using commercial kits.

Results

In MIRI rats, Dp treatment dose-dependently increased the left ventricular ejection fraction (EF) and fractional shortening (FS) while reduced the left ventricular internal diameter in diastole (LVIDd) and systole (LVIDs). The increase of necrosis and fibrosis in cardiac tissues of MIRI rats were relieved by Dp. Dp treatment inhibited the apoptosis and ferroptosis of cardiomyocytes both in vivo and in vitro. Mechanically, Dp docked with a ferroptosis-related protein ALOX15 to induce its degradation. Moreover, ferroptosis activator erastin and ALOX15 overexpression reversed the protective effects of Dp on cardiomyocytes.

Conclusion

Dp inhibited ferroptosis by molecular docking ALOX15 and inducing its degradation, thereby improving MIRI.

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飞鸽苷抑制alox15介导的大鼠铁下垂，减轻心肌缺血再灌注损伤。

目的：探讨飞燕草苷（Dp）在心肌缺血再灌注损伤（MIRI）中的作用及其机制。方法：采用左冠状动脉前降支结扎30 min，再灌注2 h，建立sd大鼠MIRI动物模型。采用氧葡萄糖剥夺/重获（OGD/R）条件模拟MIRI细胞模型，刺激原代心肌细胞和H9C2细胞。采用超声、苏木精染色、伊红染色及马松染色观察Dp治疗后大鼠心功能及心肌梗死情况。细胞计数试剂盒-8法检测细胞活力，流式细胞术检测细胞凋亡。Western blotting和定量实时聚合酶链反应检测ALOX15的表达。此外，使用商业试剂盒检测铁中毒相关因子和乳酸脱氢酶水平。结果：在MIRI大鼠中，Dp治疗剂量依赖性地增加左心室射血分数（EF）和分数缩短（FS），同时降低左心室舒张期（LVIDd）和收缩期（LVIDs）内径。Dp可减轻MIRI大鼠心肌组织坏死和纤维化的增加。Dp在体内和体外均能抑制心肌细胞凋亡和铁下垂。机械上，Dp与铁凋亡相关蛋白ALOX15对接，诱导其降解。此外，铁凋亡激活因子erastin和ALOX15过表达逆转了Dp对心肌细胞的保护作用。结论：Dp通过分子对接ALOX15，诱导其降解，从而抑制铁下垂，改善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

Biochimica et biophysica acta. Molecular cell research 生物-生化与分子生物学

CiteScore

10.00

自引率

2.00%

发文量

151

审稿时长

44 days

期刊介绍： BBA Molecular Cell Research focuses on understanding the mechanisms of cellular processes at the molecular level. These include aspects of cellular signaling, signal transduction, cell cycle, apoptosis, intracellular trafficking, secretory and endocytic pathways, biogenesis of cell organelles, cytoskeletal structures, cellular interactions, cell/tissue differentiation and cellular enzymology. Also included are studies at the interface between Cell Biology and Biophysics which apply for example novel imaging methods for characterizing cellular processes.