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

Abstract

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&#x2012;determined infarct volume. Mitochondrial ultrastructure was observed by transmission electron microscopy. Biochemical analyses quantified malondialdehyde (MDA), iron content and inflammatory cytokines (IL-1&#x3b2;, IL-6, TNF-&#x3b1;). 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&#x2009;<&#x2009;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&#x2009;<&#x2009;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&#x2009;<&#x2009;0.05). Ciprofol ameliorates CIRI in rats by inhibiting ferroptosis and inflammatory factor through upregulating AMPK.