Liraglutide Inhibits Autophagy to Ameliorate Post-Cardiac Arrest Brain Injury and Ferroptosis in Rats.

To investigate whether Liraglutide had a neuroprotective after cardiac arrest and return of spontaneous circulation (CA/ROSC) and explore its potential mechanisms. Adopting an 8-min asphyxial cardiac arrest model. Evaluate the neurological deficit score (NDS), observe pathological changes in hippocampal tissue with HE staining, and measure the expression level of proteins in hippocampal tissue with Western blot. Detection of hippocampal cell apoptosis using TUNEL (TdT-mediated dUTP Nick-End Labeling) method. Immunofluorescence staining was used to detect the expression of LC-3 in the hippocampus, and enzyme linked immunosorbent assay (ELISA) was used to detect the inflammatory factor TNF-α and IL-1β in serum and hippocampus. Autophagy and apoptosis were activated and the expressions of proteins reached significance at 24 h after CA/ROSC. Moreover, rapamycin enhanced apoptosis, ferroptosis and aggravated neuro-pathological damage while 3-methyladenine reduced that. Furthermore, liraglutide treatment improved the 7-day survival rate and NDS, reduced histological signs of injury and inhibited apoptosis, ferroptosis and inflammatory cytokines released after cardiac arrest, and these effects were offset by autophagy agonist. Liraglutide could exert a protective role against post-cardiac arrest brain injury, which could be partially mediated by inhibiting autophagy and ferroptosis. Results clearly indicate that liraglutide may attenuate post-cardiac arrest brain injury (PCABI) by anti-apoptotic and anti-inflammatory via inhibiting autophagy and ferroptosis.