5-Azacytidine is well known for its clinical usage in cancer treatments. The present study investigates the role of 5-azacytidine as a cardioprotective agent to ameliorate ischemia/reperfusion (I/R) injury. The cardioprotective effect of 5-azacytidine was evaluated in three experimental models: in vitro, ex vivo, and in vivo. The cardioprotective effect was evaluated via cell viability, hemodynamic indices, infarct size measurement, and assessment of histopathology, oxidative stress, and mitochondrial function. The experiments were repeated in the presence of PI3K/GSK3β and mitochondrial K_ATP (mtK_ATP) cardioprotective signaling pathway inhibitors to understand the underlying mechanism. 5-Azacytidine improved the cell viability by 29% in I/R-challenged H9C2 cells. Both isolated rat heart and LAD ligation model confirmed the infarct sparing effect of 5-azacytidine against I/R. It also provided a beneficial effect by normalizing the altered hemodynamics, reducing the infarct size and cardiac injury markers, reversing the perturbation of mitochondria, reduced oxidative stress, and improved the pPI3K and pAKT protein expression from I/R. In addition, it also augmented the activation of PI3K/AKT and mtK_ATP signaling pathway, confirmed by using wortmannin (PI3K inhibitor), SB216763 (GSK3β inhibitor), and glibenclamide (mtK_ATP channel closer). The effectiveness of 5-azacytidine as a cardioprotective agent is attributed to its activation of the PI3K/GSK3β and mtK_ATP channel signaling axis, thereby preserving mitochondrial function and reducing oxidative stress.

中文翻译：

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用 5-氮杂胞苷预处理大鼠心脏通过 PI3K/GSK3β 和线粒体 KATP 信号轴减轻心肌缺血/再灌注损伤

5-氮杂胞苷因其在癌症治疗中的临床应用而闻名。本研究调查了 5-氮杂胞苷作为心脏保护剂在改善缺血/再灌注 (I/R) 损伤方面的作用。在三个实验模型中评估了 5-氮杂胞苷的心脏保护作用：体外、离体和体内。通过细胞活力、血流动力学指标、梗死面积测量以及组织病理学、氧化应激和线粒体功能的评估来评估心脏保护作用。在 PI3K/GSK3β 和线粒体 K _ATP (mtK _ATP) 心脏保护信号通路抑制剂以了解其潜在机制。5-氮杂胞苷在 I/R 攻击的 H9C2 细胞中提高了 29% 的细胞活力。离体大鼠心脏和 LAD 结扎模型均证实了 5-氮杂胞苷对 I/R 的梗死保护作用。它还通过使改变的血流动力学正常化、减少梗塞面积和心脏损伤标志物、逆转线粒体的扰动、减少氧化应激以及改善 I/R 中 pPI3K 和 pAKT 蛋白的表达来提供有益效果。此外，它还增强了 PI3K/AKT 和 mtK _ATP信号通路的激活，通过使用 wortmannin（PI3K 抑制剂）、SB216763（GSK3β 抑制剂）和格列本脲（mtK _ATP通道更近）。5-氮杂胞苷作为心脏保护剂的有效性归因于其激活 PI3K/GSK3β 和 mtK _ATP通道信号轴，从而保持线粒体功能并减少氧化应激。