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Acupuncture attenuates myocardial ischemia/reperfusion injury-induced ferroptosis via the Nrf2/HO-1 pathway
Xiao Li1, Yu-Xin Sun1, Adi Wirawan Tjahjono2
1School of Acu-Mox and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, People's Republic of China.
Aims:
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.
Materials And Methods:
Firstly, Fe2+ 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.
Results:
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.
Conclusion:
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.
Insights
Electro-acupuncture (EA) protects against ferroptosis in myocardial ischemia/reperfusion injury (MIRI) by activating the Nrf2/HO-1 pathway. This study provides evidence for acupuncture
Area of Science:
- Cardiovascular Research
- Cellular Biology
- Integrative Medicine
Background:
- Myocardial ischemia/reperfusion injury (MIRI) leads to ferroptosis in cardiomyocytes, a form of cell death.
- Understanding the molecular mechanisms underlying MIRI-induced ferroptosis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the effect of electro-acupuncture (EA) on ferroptosis in MIRI.
- To determine if the Nrf2/HO-1 signaling pathway mediates the protective effects of EA.
Main Methods:
- Mice with MIRI were treated with EA or sham acupuncture (SA).
- Cardiac function, iron deposition, and levels of Nrf2 and HO-1 were assessed.
- Nrf2 inhibitor (ML385) and agonist (DMF) were used to explore pathway involvement.
Main Results:
- MIRI induced ferroptosis, evidenced by increased iron deposition and decreased Nrf2/HO-1 levels.
- EA treatment improved cardiac function, reduced iron deposition, and increased Nrf2/HO-1 levels compared to MIRI.
- EA's protective effects were partially blocked by Nrf2 inhibition.
Conclusions:
- Electro-acupuncture alleviates MIRI-induced ferroptosis in mice.
- The Nrf2/HO-1 pathway is essential for EA's cardioprotective effects in MIRI.
- This research supports acupuncture's role in treating cardiovascular diseases.
