Myocardial ischemia/reperfusion (I/R) injury contributes to the pathogenesis of numerous diseases. Based on its antioxidant and anti‑inflammatory effects, dimethyl fumarate (DMF) has been reported to exert protective effects against I/R. However, to the best of our knowledge, its potential role as a myocardial protective agent in heart disease has received little attention. Previous studies have suggested that DMF may exert its protective effects by activating nuclear factor erythroid 2‑related factor 2 (Nrf2); however, the exact underlying mechanisms remain to be elucidated. The aim of the present study was to investigate the protective role of DMF in myocardial I/R injury, and to determine the role of Nrf2 in mediating the activity of DMF. H9c2 cells were incubated with DMF (20 µM) for 24 h before establishing the I/R model, and were then subjected to myocardial ischemia for 6 h, followed by reperfusion. Cell viability, lactate dehydrogenase levels, anti‑oxidant enzyme expression levels and anti‑apoptotic effects were evaluated, and AKT/Nrf2 pathway‑associated mechanisms were investigated. The results of the present study indicated that DMF may reduce myocardial I/R injury in a Nrf2‑dependent manner. DMF significantly improved cellular viability, suppressed the expression of apoptotic markers, decreased the production of reactive oxygen species and increased the expression of Nrf2‑regulated antioxidative genes. Notably, these beneficial DMF‑mediated effects were not observed in the control or I/R groups. In conclusion, the results of the present study suggested that DMF may exert protective effects against a myocardial I/R model, and further validated Nrf2 modulation as a primary mode of action. Thus suggesting that DMF may be a potential therapeutic agent for AKT/Nrf2 pathway activation in myocardial, and potentially systemic, diseases.

中文翻译：

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富马酸二甲酯对心肌细胞氧化损伤和信号传导的保护作用。

心肌缺血/再灌注 (I/R) 损伤有助于许多疾病的发病机制。据报道，富马酸二甲酯 (DMF) 具有抗氧化和抗炎作用，可对 I/R 发挥保护作用。然而，据我们所知，它在心脏病中作为心肌保护剂的潜在作用很少受到关注。先前的研究表明，DMF 可能通过激活核因子红细胞 2 相关因子 2 (Nrf2) 发挥其保护作用；然而，确切的潜在机制仍有待阐明。本研究的目的是研究 DMF 在心肌 I/R 损伤中的保护作用，并确定 Nrf2 在介导 DMF 活性中的作用。在建立 I/R 模型之前，将 H9c2 细胞与 DMF（20 µM）孵育 24 小时，然后进行心肌缺血6小时，然后再灌注。评估了细胞活力、乳酸脱氢酶水平、抗氧化酶表达水平和抗凋亡作用，并研究了 AKT/Nrf2 通路相关机制。本研究的结果表明，DMF 可能以 Nrf2 依赖性方式减少心肌 I/R 损伤。DMF 显着提高了细胞活力，抑制了凋亡标志物的表达，减少了活性氧的产生，并增加了 Nrf2 调节的抗氧化基因的表达。值得注意的是，在对照组或 I/R 组中未观察到这些有益的 DMF 介导的效应。总之，本研究的结果表明 DMF 可能对心肌 I/R 模型发挥保护作用，并进一步验证了 Nrf2 调制作为主要作用方式。因此，表明 DMF 可能是心肌和潜在全身疾病中 AKT/Nrf2 通路激活的潜在治疗剂。