Ac 2-26 reduced pyroptosis to ameliorate the cerebral injury in rats after cardiopulmonary bypass via the AKT1-eNOS pathway

Abstract

Background: Cardiopulmonary bypass (CPB) generally results inbrain injury, which is primarily caused by inflammation. Ac2-26 protects against multiple organ injury via anti-inflammatory activities. The present study evaluated the effect of Ac2-26 on brain injury in CPB rats. Methods: A total of 40 rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The sham group only received anesthesia, intubation and cannulation, and rats in the other groups underwent the standard CPB surgery. Rats in the sham and CPB groups received saline, and rats in the Ac and Ac/AKT1 groups received Ac2-26 immediately after CPB. Rats in the Ac/AKT1 group were injected with shRNA (AKT1) 3 days before CPB. The neurological function score and brain edema were evaluated 12 hours after CPB, and brain pathological injury and hippocampal apoptosis were assessed. The levels of TNF-α, IL-1β, IL-6, IL-10, S100β and NSE were tested. AKT1, eNOS, and phosphorylated NF-κB 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 and hippocampal apoptosis. Ac2-26 also reduced the proinflammatory factorsS100β and NSE but increased IL-10. Ac2-26 decreased phosphorylated NF-κB, Bax and cleaved caspase-3 but increased Bcl-2. AKT1 shRNA significantly reversed the protective effect of Ac2-26. Conclusions: Ac2-26 significantly improved neurological function, reduced brain injury, regulated inflammation, and inhibited apoptosis after CPB. The protective effect of Ac2-26 primarily depended on AKT1.