Xia Xuefeng, Ding Yaping, Zhou Chunmei, Zhang Hanyu, Yang Xinran, Shen Chuchu, Xu Senlei, Zhang Hongru, Gu Yihuang, Bai Hua
Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing 210023, P. R. China.
College of Acupuncture and Tuina, Nanjing University of Chinese Medicine, Nanjing 210023, P. R. China.
Am J Chin Med. 2025;53(2):337-352. doi: 10.1142/S0192415X25500132. Epub 2025 Mar 20.
Oxidative stress and pyroptosis have been established as key contributors to myocardial ischemia-reperfusion injury (MIRI). While previous studies reported that electroacupuncture (EA) preconditioning exerted cardioprotective effects, the underlying mechanisms remain elusive. Thus, this study aimed to investigate the effects of EA preconditioning on oxidative stress and pyroptosis in MIRI rats, and explore the role of nuclear factor E2-associated factor 2 (Nrf2) throughout that process. A MIRI model was constructed by ligating the left anterior descending coronary artery for 30 min, followed by 4 h of reperfusion in rats. Prior to modeling, rats were subjected to EA at the Neiguan Point for three days. Furthermore, ML385, a Nrf2 inhibitor, was administered in order to examine the role of Nrf2 in regulating oxidative stress and pyroptosis following EA preconditioning. The results revealed that EA preconditioning improved left ventricular function after MIRI and reduced both the myocardial infarction area and cTnT levels. Meanwhile, EA preconditioning alleviated MIRI-induced oxidative stress and pyroptosis, as evidenced by the downregulation of ROS, MDA, NF-κB p65, caspase-1, IL-1β, and GSDMD-N, and the upregulation of SOD and HO-1. Mechanistically, EA up-regulated enhanced the expression of Nrf2. However, its cardioprotective effects and ability to attenuate oxidative stress and pyroptosis were suppressed by the inhibition of Nrf2. Taken together, our study indicated that EA preconditioning attenuated MIRI in rats by mitigating oxidative stress and pyroptosis, with Nrf2 playing a vital role in this protective mechanism.
氧化应激和细胞焦亡已被确认为心肌缺血再灌注损伤（MIRI）的关键促成因素。虽然先前的研究报道电针（EA）预处理具有心脏保护作用，但其潜在机制仍不清楚。因此，本研究旨在探讨EA预处理对MIRI大鼠氧化应激和细胞焦亡的影响，并探究核因子E2相关因子2（Nrf2）在整个过程中的作用。通过结扎大鼠左冠状动脉前降支30分钟，然后再灌注4小时构建MIRI模型。在建模前，大鼠在双侧内关穴接受三天的电针治疗。此外，给予Nrf2抑制剂ML385，以研究Nrf2在EA预处理后调节氧化应激和细胞焦亡中的作用。结果显示，EA预处理改善了MIRI后大鼠的左心室功能，减小了心肌梗死面积并降低了cTnT水平。同时，EA预处理减轻了MIRI诱导的氧化应激和细胞焦亡，表现为ROS、MDA、NF-κB p65、caspase-1、IL-1β和GSDMD-N的下调以及SOD和HO-1的上调。机制上，EA上调增强了Nrf2的表达。然而，Nrf2的抑制削弱了其心脏保护作用以及减轻氧化应激和细胞焦亡的能力。综上所述，我们的研究表明，EA预处理通过减轻氧化应激和细胞焦亡减轻大鼠MIRI，Nrf2在这一保护机制中起关键作用。
