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.
Objective DNA methylation plays an important role in inflammation and oxidative stress. This study aimed to investigate the effect of inhibiting DNA methylation on lung ischemia–reperfusion injury (LIRI). Methods We adopted a completely random design for our study. Thirty-two rats were randomized into the sham, LIRI, azathioprine (AZA), and pluripotin (SC1) groups. The rats in the LIRI, AZA, and SC1 groups received left lung transplantation and intravenous injection of saline, AZA, and SC1, respectively. After 24 hours of reperfusion, histological injury, the arterial oxygen partial pressure to fractional inspired oxygen ratio, the wet/dry weight ratio, protein and cytokine concentrations in lung tissue, and DNA methylation in lung tissue were evaluated. The pulmonary endothelium that underwent hypoxemia and reoxygenation was treated with AZA or SC1. Endothelial apoptosis, chemokines, reactive oxygen species, nuclear factor-κB, and apoptotic proteins in the endothelium were studied. Results Inhibition of DNA methylation by AZA attenuated lung injury, inflammation, and the oxidative stress response, but SC1 aggravated LIRI injury. AZA significantly improved endothelial function, suppressed apoptosis and necrosis, reduced chemokines, and inhibited nuclear factor-κB. Conclusions Inhibition of DNA methylation ameliorates LIRI and apoptosis and improves pulmonary function via the regulation of inflammation and oxidative stress.
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