[Electroacupuncture at "Xinshu" (BL15) improves myocardial ischemia by inhibiting the ferroptosis pathway in rats].

Electroacupuncture at BL15 reversed the ECG ST-segment abnormalities induced by isoproterenol-modeled myocardial ischemia in rats.

• 18 male SD rats were randomly divided into control, model, and EA groups (n=6 each).
• MI model was established by subcutaneous injection of isoproterenol (ISO, 60 mg/kg) for 2 consecutive days.
• EA was applied to bilateral BL15 for 30 min, once a day for 3 days.
• The model group showed significant ST-segment elevation after modeling and depression after intervention compared to control (P<0.01); EA reversed these ST-segment changes compared to the model group (P<0.01).
• ECG was recorded using standard limb lead II via a multi-channel physiological recorder.

Myocardial ischemia induced by isoproterenol caused significant histopathological and ultrastructural damage to cardiomyocytes and their mitochondria, which was attenuated by electroacupuncture.

• HE staining revealed reduction in cardiomyocyte number, loose arrangement, extracellular inflammatory cell infiltration, vacuolated myocardial fibers, and increased extracellular space in the model group.
• Transmission electron microscopy (TEM) showed decreased mitochondrial volume, increased mitochondrial density, and breakage of cristae in the model group.
• The EA group showed relatively milder injury in both cardiomyocytes and their mitochondria compared to the model group.

Isoproterenol-induced myocardial ischemia significantly increased myocardial Fe2+ content and decreased glutathione (GSH) levels and antioxidant enzyme activities, all of which were reversed by electroacupuncture at BL15.

• Compared with the control group, the model group showed a significant increase in Fe2+ content (P<0.01) and significant decreases in GSH content and SOD and GSH-PX activities (P<0.01).
• EA treatment significantly decreased Fe2+ content compared to the model group (P<0.05).
• EA treatment significantly increased GSH content and SOD and GSH-PX activities compared to the model group (P<0.01 or P<0.05).
• Biochemical detection methods were used to measure Fe2+, MDA, GSH, SOD, and GSH-PX in myocardial tissue.

The model group exhibited downregulation of ferroptosis-protective markers (FTH1, Nrf2, SLC7A11, GPX4) and upregulation of the ferroptosis-promoting marker ACSL4 in myocardial tissue, which were reversed by electroacupuncture.

• Compared with the control group, the model group showed significantly decreased mRNA and protein expression of FTH1, Nrf2, SLC7A11, and GPX4 (P<0.01), and significantly increased ACSL4 mRNA and protein expression (P<0.05).
• Compared with the model group, EA significantly increased FTH1, Nrf2, SLC7A11, and GPX4 mRNA and protein expression (P<0.01 or P<0.05) and decreased ACSL4 mRNA and protein expression (P<0.05 or P<0.01).
• Gene expression was measured by real-time fluorescence quantitative PCR and protein expression by Western blot.
• These molecular changes are consistent with inhibition of the ferroptosis signaling pathway.

Electroacupuncture at BL15 modulates the ferroptosis pathway in myocardial cells as a proposed mechanism of cardioprotection in myocardial ischemia.

• The study investigated ferroptosis-related markers including iron metabolism (Fe2+, FTH1), oxidative stress (MDA, GSH, SOD, GSH-PX), and key regulatory proteins (Nrf2, SLC7A11, GPX4, ACSL4).
• The pattern of molecular changes (reduced Fe2+, increased GPX4/SLC7A11/Nrf2/FTH1, decreased ACSL4) is consistent with suppression of ferroptosis.
• The authors concluded that 'EA at BL15 can alleviate ischemic myocardium injury in rats with MI, which may be achieved by inhibiting the ferroptosis signaling pathway in the myocardial cells.'