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

May 12, 2025

Experts: Chengjun Xing,Xin Fan,Mudi Liu,Ye Chen,Jing Jia,Wei Li,Hong Yu,Jun Zhou

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.
© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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ABOUT THE EXPERTS

Chengjun Xing,Xin Fan,Mudi Liu,Ye Chen,Jing Jia,Wei Li,Hong Yu,Jun Zhou

Chengjun Xing

Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou, 646000, Sichuan, China.

Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, People’s Republic of China.

Xin Fan

Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou, 646000, Sichuan, China.

Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, People’s Republic of China.

Mudi Liu

Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou, 646000, Sichuan, China.

Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, People’s Republic of China.

Ye Chen

Department of Traditional Chinese Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China.

Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, People’s Republic of China.

Jing Jia

Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou, 646000, Sichuan, China.

Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, People’s Republic of China.

Wei Li

Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, People’s Republic of China.

Department of Anesthesiology, He Jiang People’s Hospital, Luzhou, 646200, People’s Republic of China.

Hong Yu

Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou, 646000, Sichuan, China. anesth-yuhong@swmu.edu.cn.

Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, People’s Republic of China. anesth-yuhong@swmu.edu.cn.

Jun Zhou

Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, No.25 Taiping Street, Luzhou, 646000, Sichuan, China. junzhou@swmu.edu.cn.

Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, People’s Republic of China. junzhou@swmu.edu.cn.