Li Xiao, Sun Yu-Xin, Tjahjono Adi Wirawan, Wei Ying, Li Xiang, Zheng Qian-Hua, Qi Wen-Chuan, Liang Fan-Rong
School of Acu-Mox and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.
School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.
Chin Med. 2025 May 9;20(1):61. doi: 10.1186/s13020-025-01114-0.
To observe the effect of electro-acupuncture (EA) on cardiomyocytes ferroptosis induced by myocardial ischemia/reperfusion injury (MIRI) in mice and to investigate whether this effect occurs via the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signalling pathway.
Firstly, Fe in the hearts and serum of mice from both the sham-operated (SO) group and MIRI group was measured to ascertain whether ferroptosis had occurred in the cardiomyocytes of mice in MIRI group. In the second phase, EA was administered, with sham acupuncture (SA) group as the comparator, to investigate the protective effects of EA on ferroptosis in MIRI cardiomyocytes and cardiac function. Additionally, we studied the levels of Nrf2 and HO-1 within the myocardium. In the third phase, Nrf2 inhibitor ML385 and agonist DMF were applied to observe the impact of inhibiting Nrf2 on the therapeutic efficacy of EA.
Compared with SO group, MIRI group showed increased iron deposition, along with a significant decrease in Nrf2 and HO-1 levels. Compared with MIRI group, MIRI + EA group exhibited significantly improved cardiac function and reduced cardiac iron deposition, accompanied by increased Nrf2 and HO-1 levels. Furthermore, the therapeutic effect of MIRI + EA group was superior to that of MIRI + SA group. Administration of ML385 partially blocked the anti-ferroptotic and cardioprotective effects of EA, while EA treatment exhibited similar effects to dimethyl fumarate (DMF) intervention.
EA alleviates ferroptosis-induced damage in MIRI in mice via the Nrf2/HO-1 pathway, providing modern scientific evidence for the application of acupuncture in the treatment of cardiovascular diseases.
观察电针(EA)对小鼠心肌缺血/再灌注损伤(MIRI)诱导的心肌细胞铁死亡的影响,并探讨这种作用是否通过核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路发生。
首先,测量假手术(SO)组和MIRI组小鼠心脏和血清中的铁,以确定MIRI组小鼠心肌细胞中是否发生了铁死亡。在第二阶段,以假针刺(SA)组为对照,给予EA,以研究EA对MIRI心肌细胞铁死亡和心脏功能的保护作用。此外,我们研究了心肌组织中Nrf2和HO-1的水平。在第三阶段,应用Nrf2抑制剂ML385和激动剂DMF,观察抑制Nrf2对EA治疗效果的影响。
与SO组相比,MIRI组铁沉积增加,Nrf2和HO-1水平显著降低。与MIRI组相比,MIRI+EA组心脏功能显著改善,心脏铁沉积减少,同时Nrf2和HO-1水平升高。此外,MIRI+EA组的治疗效果优于MIRI+SA组。给予ML385部分阻断了EA的抗铁死亡和心脏保护作用,而EA治疗表现出与富马酸二甲酯(DMF)干预相似的效果。
EA通过Nrf2/HO-1途径减轻小鼠MIRI中铁死亡诱导的损伤,为针刺在心血管疾病治疗中的应用提供了现代科学依据。