Metformin ameliorates blunted cardioprotective response of ischemic postconditioning in rats subjected to high fat diet.

IF 2.5 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS

Acta cardiologica Pub Date : 2025-08-12 DOI:10.1080/00015385.2025.2538399

Satnam Singh, Kuldeep Kumar, Ayush Kandpal, Harlokesh Narayan Yadav, Leonid Maslov, Amteshwar Singh Jaggi, Nirmal Singh

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Abstract

Background: Cardioprotective response of ischaemic postconditioning (iPoCo) is blunted in conditions of vascular endothelial dysfunction (ED) associated with hypercholesterolaemia, diabetes, hypertension, etc.

Objective: The current study investigates the effect of metformin on the blunted cardioprotective response of iPoCo in rats subjected to high fat diet (HFD).

Methodology: Wistar rats were subjected to HFD for 56 days. Myocardial ischaemia-reperfusion (I/R) injury was induced by subjecting the heart to global ischaemia of 30 min followed by reperfusion of 120 min after mounting on Langendorff Power Lab apparatus. iPoCo consisting of 6 alternative cycles of ischaemia and reperfusion of 10 sec each, was given after the global ischaemia at the onset of reperfusion. Metformin (25 µM and 50 µM) treatment was given after the global ischaemia just before reperfusion. Myocardial injury was assessed by estimation of infarct size, specific biomarkers of myocardial injury, oxidative stress, inflammation and hemodynamic index.

Results: HFD animal showed significant rise in serum total cholesterol and nitrate levels reflecting hypercholesterolaemia and ED. I/R produced significant myocardial damage indicated by an increase in infarct size, specific biomarkers (LDH, CK-MB, cTn I), oxidative stress- inflammatory parameters (heart Nrf-2, TBARS, TNF-α and decreased GSH and catalase levels) and altered hemodynamic index. iPoCo significantly alleviated I/R induced myocardial injury with respect to above parameters in normal rats but failed to produce such an effect in HFD rats. Treatment of metformin (25 µM and 50 µM) not only mimicked the cardioprotective effect of iPoCo in normal rats but also restored the lost effect of iPoCo in HFD rats.

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二甲双胍改善高脂饮食大鼠缺血后适应的钝化心脏保护反应。

背景：高胆固醇血症、糖尿病、高血压等相关血管内皮功能障碍（ED）导致缺血后适应（iPoCo）心肌保护反应减弱。目的：研究二甲双胍对高脂饮食（HFD）大鼠缺血后适应（iPoCo）心肌保护反应减弱的影响。方法：Wistar大鼠经HFD处理56 d。心肌缺血-再灌注（I/R）损伤是在Langendorff Power Lab仪器上安装后，心脏局部缺血30min，再灌注120min。缺血再灌注开始后给予iPoCo，包括缺血再灌注交替6个周期，每个周期10秒。全身缺血后再灌注前给予二甲双胍（25µM和50µM）治疗。通过估计梗死面积、心肌损伤特异性生物标志物、氧化应激、炎症和血流动力学指数来评估心肌损伤。结果：HFD动物血清总胆固醇和硝酸盐水平显著升高，反映了高胆固醇血症和ED。I/R产生显著的心肌损伤，表现为梗死面积增加、特异性生物标志物（LDH、CK-MB、cTn I）、氧化应激-炎症参数（心脏Nrf-2、TBARS、TNF-α和GSH和过氧化氢酶水平降低）和血流动力学指数改变。iPoCo对正常大鼠I/R诱导的心肌损伤均有明显的缓解作用，但对HFD大鼠无明显影响。二甲双胍（25µM和50µM）不仅可以模拟iPoCo对正常大鼠的心脏保护作用，而且可以恢复iPoCo在HFD大鼠中失去的作用。

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

Acta cardiologica 医学-心血管系统

CiteScore

2.50

自引率

12.50%

发文量

115

审稿时长

2 months

期刊介绍： Acta Cardiologica is an international journal. It publishes bi-monthly original, peer-reviewed articles on all aspects of cardiovascular disease including observational studies, clinical trials, experimental investigations with clear clinical relevance and tutorials.