Alpinetin通过线粒体铁蛋白抑制铁下垂和细胞凋亡，对心肌缺血再灌注损伤具有保护作用

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology Pub Date : 2025-09-05 DOI:10.1016/j.ejphar.2025.178123

Chenchao Zou , Fajia Hu , Xiuqi Wang , Lanxiang Liu , Huaxi Zou , Jichun Liu , Songqing Lai , Huang Huang

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引用次数: 0

摘要

目的心肌梗死后的化学-再灌注损伤仍然是一个主要问题。据报道，ALPT具有心脏保护作用以及对缺血再灌注损伤的抵抗作用。然而，其在心肌缺血再灌注损伤中的作用和机制尚不清楚。方法采用H9c2细胞缺氧/再氧合（A/R）损伤模型和Sprague-Dawley大鼠缺血再灌注（I/R）损伤模型。采用多指标评价、流式细胞术、western blot、透射电镜等方法评价高松素预处理的保护作用及其作用机制。此外，我们还利用pAD/FTMT- shrna研究了线粒体铁蛋白（FTMT）在基于高山素的保护中的作用。实验结果最终在大鼠I/R损伤模型中得到验证。结果与他汀-1类似，在损伤模型中，alpinetin降低前列腺素内过氧化物合成酶2 （PTGS2）、乳酸脱氢酶、丙二醛、亚铁、活性氧和氧化谷胱甘肽二硫（GSSG）水平，提高细胞活力、谷胱甘肽（GSH）水平、GSH/GSSG比值和谷胱甘肽过氧化物酶4蛋白水平。Alpinetin还能逆转A/R损伤诱导的caspase-3活性和凋亡率升高，Bcl-2/Bax比值和线粒体膜电位水平降低。值得注意的是，高松素可以减轻A/R损伤引起的线粒体损伤。这些保护作用通过FTMT沉默被阻断。结论肾上腺素对心肌缺血-再灌注损伤的保护作用可能与抑制铁下垂和细胞凋亡有关。

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Alpinetin protects against myocardial ischemia–reperfusion injury by inhibiting ferroptosis and apoptosis via mitochondrial ferritin

Purpose

Ischemia–reperfusion injury remains a major problem following myocardial infarction. Alpinetin (ALPT) has been reported to exhibit cardioprotective effects as well as resistance to ischemia–reperfusion injury. However, its role and mechanism during myocardial ischemia–reperfusion injury are unknown.

Methods

The anoxia/reoxygenation (A/R) injury model of H9c2 cells and the ischemia reperfusion (I/R) injury model of Sprague-Dawley rats were used in this study. Multiple indicator evaluations, flow cytometry, western blot, and transmission electron microscopy were performed to assess the protective effect of alpinetin pretreatment and its mechanism of action. In addition, the role of mitochondrial ferritin (FTMT) in alpinetin-based protection was investigated using pAD/FTMT-shRNA. The experimental findings were ultimately validated in rat I/R injury models.

Results

Similar to ferrostatin-1, alpinetin decreased prostaglandin-endoperoxide synthase 2 (PTGS2), lactate dehydrogenase, malondialdehyde, ferrous iron, reactive oxygen species, and oxidized glutathione disulfide (GSSG) levels and increased cell viability, glutathione (GSH) levels, the GSH/GSSG ratio, and glutathione peroxidase 4 protein levels in the injury models. Alpinetin also reversed A/R injury-induced increased caspase-3 activity and apoptosis rate and decreased Bcl-2/Bax ratio and mitochondrial membrane potential level. Of note, alpinetin attenuated mitochondrial damage induced by A/R injury. These protective effects were blocked via FTMT silencing.

Conclusion

Alpinetin protects against myocardial ischemia–reperfusion injury by inhibiting ferroptosis and apoptosis via FTMT.

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来源期刊

European journal of pharmacology 医学-药学

CiteScore

9.00

自引率

0.00%

发文量

572

审稿时长

34 days

期刊介绍： The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.