Ac2-26 activated the AKT1/GSK3β pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass.

Autor: Ju YN; Department of Intensive Care Unit, Hainan General Hospital (Hainan Affiliated Hosptial of Hainan Medical University), Clinical College, Hainan Medical University, Haikou, 570311, China., Zou ZW; Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150081, China., Jia BW; Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150081, China., Liu ZY; Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150081, China., Sun XK; Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150081, China., Qiu L; Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150081, China., Gao W; Department of Anesthesiology, Hainan General Hospital (Hainan Affiliated Hosptial of Hainan Medical University), Clinical College, Hainan Medical University, Haikou, 570311, China. gaowei20055@126.com.
Jazyk: angličtina
Zdroj: BMC cardiovascular disorders [BMC Cardiovasc Disord] 2024 May 21; Vol. 24 (1), pp. 266. Date of Electronic Publication: 2024 May 21.
DOI: 10.1186/s12872-024-03909-9
Abstrakt: Background: Cardiopulmonary bypass (CPB) results in brain injury, which is primarily caused by inflammation. Ac2-26 protects against ischemic or hemorrhage brain injury. The present study was to explore the effect and mechanism of Ac2-26 on brain injury in CPB rats.
Methods: Forty-eight rats were randomized into sham, CPB, Ac, Ac/AKT1, Ac/GSK3βi and Ac/AKT1/GSK3βa groups. Rats in sham group only received anesthesia and in the other groups received standard CPB surgery. Rats in the sham and CPB groups received saline, and rats in the Ac, Ac/AKT1, Ac/GSK3βi and Ac/AKT1/GSK3βa groups received Ac2-26 immediately after CPB. Rats in the Ac/AKT1, Ac/GSK3βi and Ac/AKT1/GSK3βa groups were injected with shRNA, inhibitor and agonist of GSK3β respectively. The neurological function score, brain edema and histological score were evaluated. The neuronal survival and hippocampal pyroptosis were assessed. The cytokines, activity of NF-κB, S100 calcium-binding protein β(S100β) and neuron-specific enolase (NSE), and oxidative were tested. The NLRP3, cleaved-caspase-1 and cleaved-gadermin D (GSDMD) in the brain were also detected.
Results: Compared to the sham group, all indicators were aggravated in rats that underwent CPB. Compared to the CPB group, Ac2-26 significantly improved neurological scores and brain edema and ameliorated pathological injury. Ac2-26 reduced the local and systemic inflammation, oxidative stress response and promoted neuronal survival. Ac2-26 reduced hippocampal pyroptosis and decreased pyroptotic proteins in brain tissue. The protection of Ac2-26 was notably lessened by shRNA and inhibitor of GSK3β. The agonist of GSK3β recovered the protection of Ac2-26 in presence of shRNA.
Conclusions: Ac2-26 significantly improved neurological function, reduced brain injury via regulating inflammation, oxidative stress response and pyroptosis after CPB. The protective effect of Ac2-26 primarily depended on AKT1/ GSK3β pathway.
(© 2024. The Author(s).)
Databáze: MEDLINE
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