Sun Qing, Lv Mei, Wang Zhen
Department of Cardiology, Yantaishan Hospital, No.10087, Science and Technology Avenue, Laishan District, Yantai 264000, Shandong, China.
General Medicine Department, Yantaishan Hospital, No.10087, Science and Technology Avenue, Laishan District, Yantai 264000, Shandong, China.
Biochim Biophys Acta Mol Cell Res. 2025 Oct;1872(7):120006. doi: 10.1016/j.bbamcr.2025.120006. Epub 2025 Jun 11.
The present study aimed to investigate the role of delphinidin (Dp) in myocardial ischemia-reperfusion injury (MIRI) and elucidate the underlying mechanism.
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.
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.
Dp inhibited ferroptosis by molecular docking ALOX15 and inducing its degradation, thereby improving MIRI.
本研究旨在探讨飞燕草素（Dp）在心肌缺血再灌注损伤（MIRI）中的作用，并阐明其潜在机制。
通过结扎左冠状动脉前降支（LAD）30分钟并再灌注2小时，在Sprague-Dawley大鼠中建立MIRI动物模型。通过氧糖剥夺/复氧（OGD/R）条件刺激原代心肌细胞和H9C2细胞，以模拟MIRI细胞模型。使用超声、苏木精-伊红染色和Masson染色评估Dp处理后大鼠的心脏功能和心肌梗死情况。分别进行细胞计数试剂盒-8检测和流式细胞术以检测细胞活力和凋亡。通过蛋白质免疫印迹法和定量实时聚合酶链反应测量ALOX15的表达。此外，使用商业试剂盒检测铁死亡相关因子和乳酸脱氢酶水平。
在MIRI大鼠中，Dp治疗剂量依赖性地增加左心室射血分数（EF）和缩短分数（FS），同时减小舒张末期（LVIDd）和收缩末期（LVIDs）的左心室内径。Dp减轻了MIRI大鼠心脏组织中坏死和纤维化的增加。Dp治疗在体内和体外均抑制了心肌细胞的凋亡和铁死亡。机制上，Dp与铁死亡相关蛋白ALOX15结合以诱导其降解。此外，铁死亡激活剂艾拉司丁和ALOX15过表达逆转了Dp对心肌细胞的保护作用。
Dp通过与ALOX15分子对接并诱导其降解来抑制铁死亡，从而改善MIRI。
