Electroacupuncture Preconditioning Attenuates Myocardial Ischemia-Reperfusion Injury in Rats Partially Through Nrf2-Mediated Reduction of Oxidative Stress and Pyroptosis.

Abstract

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.