Tekiyeh Maroof Neda, Mehrzadi Saeed, Naseroleslami Maryam, Aboutaleb Nahid
Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
J Cardiovasc Transl Res. 2025 Feb 19. doi: 10.1007/s12265-025-10597-z.
Although apelin-13 has cardioprotective impact, its short half-life in the bloodstream has challenged its clinical application. Using nanocarriers can increase the bioavailability, functionality, and stability of drugs. Current investigation aims to find whether apelin13-loaded nano-niosomes confer cardioprotection in an animal model of myocardial ischemia/reperfusion injury (MI/R) via suppressing ferroptosis, targeting Nrf2 pathway, and AMPK/GSK-3β axis. Ligation of the left anterior coronary artery descending was done to establish the MI/R model and 15 μg/kg of apelin13-loaded nano-niosomes were intramyocardially administrated. Echocardiography, RT-PCR, immunohistochemistry, western blot, ELISA kits, and H&E staining were applied to measure the related indicators. Treatment with both apelin13 and apelin13 loaded nano-niosomes could improve cardiac function and attenuate oxidative stress, myocardial inflammatory factors, and hence ferroptosis by activating the Nrf2 and its downstream proteins HO1, NQO1, AMPK/GSK-3β signaling pathway. In conclusion, apelin13-loaded nano-niosomes are effective MI therapeutic agents against MI/R-induced ferroptosis by activation of Nrf2 via AMPK/GSK-3β axis.
尽管apelin-13具有心脏保护作用，但其在血液中的半衰期较短，这对其临床应用构成了挑战。使用纳米载体可以提高药物的生物利用度、功能和稳定性。当前的研究旨在探究负载apelin13的纳米非离子表面活性剂囊泡是否通过抑制铁死亡、靶向Nrf2途径和AMPK/GSK-3β轴，在心肌缺血/再灌注损伤（MI/R）动物模型中发挥心脏保护作用。通过结扎左冠状动脉前降支来建立MI/R模型，并向心肌内注射15μg/kg负载apelin13的纳米非离子表面活性剂囊泡。应用超声心动图、逆转录聚合酶链反应（RT-PCR）、免疫组织化学、蛋白质免疫印迹法、酶联免疫吸附测定试剂盒（ELISA试剂盒）和苏木精-伊红（H&E）染色来测量相关指标。apelin13和负载apelin13的纳米非离子表面活性剂囊泡治疗均可通过激活Nrf2及其下游蛋白血红素加氧酶1（HO1）、醌氧化还原酶1（NQO1）、AMPK/GSK-3β信号通路来改善心脏功能，减轻氧化应激、心肌炎性因子，从而减轻铁死亡。总之，负载apelin13的纳米非离子表面活性剂囊泡是通过AMPK/GSK-3β轴激活Nrf2来有效对抗MI/R诱导的铁死亡的心肌梗死治疗药物。
