[Effects of acupuncture on ferroptosis and ferritinophagy in cerebral ischemia-reperfusion rats based on KAT3B/ACSL4 pathway].

The CIRI model group showed significantly increased neurological deficit scores, cerebral infarction volume, and blood-brain barrier permeability compared to the sham operation group.

• Neurological deficit score, cerebral infarction volume, and Evans blue permeability were all significantly increased in the model group (P<0.01).
• Model was established by middle cerebral artery occlusion in male SD rats.
• 40 male SD rats were divided into 4 groups of 10: sham operation, model, acupuncture, and western medicine.

CIRI caused significant neuronal structural damage and increased apoptosis in the ischemic cerebral cortex.

• Histopathological changes included cell necrosis, nuclear shrinkage, loss of cytoplasm, and a decrease in Nissl bodies (P<0.01).
• TUNEL-positive cells were significantly increased in the model group compared to sham operation (P<0.01).
• NeuN expression was decreased, while NCOA4 and LC3B expressions were increased in the ischemic cerebral cortex (P<0.01).

CIRI resulted in significant mitochondrial damage in neurons of the ischemic cerebral cortex.

• Transmission electron microscopy revealed loss of mitochondrial integrity, mitochondrial enlargement, cristae rupture, and vacuolization in the model group.
• These mitochondrial changes are consistent with ferroptosis-associated morphology.

CIRI significantly elevated oxidative stress markers and ferroptosis-related indicators in ischemic brain tissue.

• Contents of ROS, Fe2+, LPO, and MDA were significantly increased in the model group compared to sham operation (P<0.01).
• GSH content and SOD activity were significantly reduced in the model group (P<0.01).
• Protein expression levels of KAT3B, ACSL4, NCOA4, and TfR1 were elevated, while GPX4, SLC7A11, FTH1, and FPN-1 were reduced (P<0.01).

Acupuncture at GV20, EX-HN1, and GV26 reversed all ferroptosis, ferritinophagy, and injury indicators in CIRI rats.

• Compared with the model group, the acupuncture group showed reversal of neurological deficit score, infarct volume, Evans blue permeability, histopathological changes, TUNEL-positive cells, ROS, Fe2+, LPO, MDA, GSH, SOD, and all measured proteins (P<0.05).
• Acupuncture was administered at 'Baihui' (GV20), 'Sishencong' (EX-HN1), and 'Shuigou' (GV26) acupoints with needles retained for 30 min, once daily for 7 consecutive days.
• NeuN expression was restored and NCOA4/LC3B expressions were reduced by acupuncture treatment (P<0.05).
• KAT3B and ACSL4 protein expression levels were reduced, while GPX4, SLC7A11, FTH1, and FPN-1 were increased by acupuncture (P<0.05).

Acupuncture showed comparable efficacy to edaravone dexborneol (western medicine) in treating CIRI.

• There was no statistically significant difference between the acupuncture group and the western medicine group on any measured indicator.
• The western medicine group received intraperitoneal injections of edaravone dexborneol at 0.29 mL·100g⁻¹·d⁻¹ for 7 consecutive days.
• Both acupuncture and western medicine groups demonstrated reversal of all measured indicators compared to the model group (P<0.05).

Acupuncture's protective effects against ferroptosis and ferritinophagy in CIRI may be mediated through inactivation of the KAT3B/ACSL4 pathway.

• KAT3B (lysine acetyltransferase 3B) and ACSL4 (acyl-CoA synthetase long-chain family member 4) protein expressions were elevated in CIRI and reduced by acupuncture treatment.
• NCOA4 (nuclear receptor coactivator 4) and TfR1 (transferrin receptor 1), key mediators of ferritinophagy, were also modulated by acupuncture.
• FTH1 (ferritin heavy chain 1) and FPN-1 (ferroportin-1) expressions were restored by acupuncture, indicating improved iron homeostasis.