Ciprofol attenuates cerebral Ischemia‒reperfusion injury in rats by inhibiting ferroptosis through upregulating AMPK

This study assesses the neuroprotective effects and molecular mechanisms of ciprofol against cerebral ischemia-reperfusion injury (CIRI) in rats. From July 2023 and July 2024, fifty male SD rats were randomly divided into five groups: control, model, ciprofol (Ci), erastin (Era), and compound C (CC). The model was induced by MCAO/R. Control group received identical surgical interventions without filament insertion. Rats neurological deficits were quantified using modified Garcia JH scores. Histopathological changes were evaluated through Nissl staining and TTC‒determined infarct volume. Mitochondrial ultrastructure was observed by transmission electron microscopy. Biochemical analyses quantified malondialdehyde (MDA), iron content and inflammatory cytokines (IL-1β, IL-6, TNF-α). Western blotting measured AMPK phosphorylation and ferroptosis proteins (GPX4, ACSL4). Relative to the model group rats, the Ci rats exhibited elevated modified Garcia JH scores (P < 0.05) accompanied by attenuated neuronal/mitochondrial damage and diminished infarct areas. Biochemical analyses revealed significant reductions in MDA, inflammatory cytokines, and ACSL4 protein expression in Ci rats, concurrent with enhanced GPX4 levels and elevated p-AMPK/T-AMPK ratios (P < 0.05). Notably, Era specimens demonstrated GPX4 downregulation with corresponding ACSL4 and iron accumulation compared to the Ci rats. Furthermore, the CC rats displayed decreased p-AMPK/T-AMPK activation relative to Ci rats (P < 0.05). Ciprofol ameliorates CIRI in rats by inhibiting ferroptosis and inflammatory factor through upregulating AMPK.