Background: Acute respiratory distress syndrome (ARDS) is characterized by severe local and systemic inflammation. Ac2-26, an Annexin A1 Peptide, can reduce the lung injury induced by reperfusion via the inhibition of inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 in ARDS. Methods: Thirty-two rats were anaesthetized and randomized into four groups: sham (S), ARDS (A), ARDS/Ac2-26 (AA), and ARDS/Ac2-26/BOC-2 (AAB) groups. Rats in the S group received saline for intratracheal instillation, while rats in the other three groups received endotoxin for intratracheal instillation, in order to prepare the ARDS and inject the saline, Ac2-26, and Ac2-26 combined with BOC-2. After 24 h, the PaO 2 /FiO 2 ratio was calculated. The lung tissue wet-to-dry weight ratio and the protein level in bronchoalveolar lavage fluid (BALF) were tested. Then, the cytokines in BALF and serum, and the inflammatory cells in BALF were investigated. Afterwards, the oxidative stress response and histological injury was evaluated. Subsequently, the epithelium was cultured and analyzed to estimate the effect of Ac2-26 on apoptosis. Results: Compared to the S group, all indexes worsened in the A, AA, and AAB groups. Furthermore, compared to the S group, Ac2-26 significantly improved the lung injury and alveolar-capillary permeability, and inhibited the oxidative stress response. In addition, Ac2-26 reduced the local and systemic inflammation through the regulation of pro-and anti-inflammatory cytokines, and the decrease in inflammatory cells in BALF. Moreover, Ac2-26 inhibited the epithelium apoptosis induced by LPS through the modulation of apoptosis-regulated proteins. The protective effect of Ac2-26 on ARDS was partially reversed by the FPR inhibitor, BOC-2. Conclusion: Ac2-26 reduced the lung injury induced by LPS, promoted alveolar-capillary permeability, ameliorated the local and systemic inflammation, and inhibited the oxidative stress response and apoptosis. The protection of Ac2-26 on ARDS was mainly dependent on the FPR pathway.

Purpose: Although mechanical ventilation is an essential support for acute respiratory distress syndrome (ARDS), ventilation also leads to ventilator-induced lung injury (VILI). This study aimed to estimate the effect and mechanism of Annexin A1 peptide (Ac2-26) on VILI in ARDS rats. Methods: Thirty-two rats were randomized into the sham (S), mechanical ventilation (V), mechanical ventilation/ Ac2-26 (VA), and mechanical ventilation/Ac2-26/L-NIO (VAL) groups. The S group only received anesthesia, and the other three groups received endotoxin and then ventilation for 4 h. Rats in the V, VA and VAL groups received saline, Ac2-26, and A c2-26/N5-(1-iminoethyl)l-ornithine (L-NIO), respectively. Results: All indexes deteriorated in the V, VA and VAL groups compared with the S group. Compared with V group, the PaO 2 /FiO 2 ratio was increased, but the wet-to-dry weight ratio and protein levels in bronchoalveolar lavage fluid were decreased in the VA group. The inflammatory cells and proinflammatory factors were reduced by Ac2-26. The oxidative stress response, lung injury and apoptosis were also decreased by Ac2-26 compared to V group. All improvements of Ac2-26 were partly reversed by L-NIO. Conclusion: Ac2-26 mitigates VILI in ARDS rats and partly depended on the endothelial nitric oxide synthase pathway.

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.

Background Although mechanical ventilation is an essential support for acute respiratory distress syndrome (ARDS), ventilation also leads to ventilator-induced lung injury (VILI). This study aimed to estimate the effect and mechanism of Annexin A1 peptide (Ac2-26) on VILI in ARDS rats. Methods Thirty-two rats were randomized into the sham (S), mechanical ventilation (V), mechanical ventilation/Ac2-26 (VA) and mechanical ventilation/Ac2-26/L-NIO (VAL) groups. The S group only received anesthesia, and the other 3 groups received endotoxin and then ventilation for 4 h. Rats in the V, VA and VAL groups received saline, Ac2-26 and A c2-26/L-NIO, respectively. The gas exchange and capillary permeability were detected. The pulmonary and systemic inflammation were investigated. The oxidative stress response was also detected. Histological injury and apoptosis in lung tissues were tested. Moreover, the epithelial cells were also cultured to detect the effect of Ac2-26 on apoptosis induced by ARDS. Results All indexes deteriorated in the V, VA and VAL groups compared with the S group. Compared with V group, the PaO2/FiO2 ratio was increased, but the wet-to-dry weight ratio and protein levels in BALF were decreased in the VA group. The inflammatory cells and proinflammatory factors were reduced by Ac2-26. The oxidative stress response, lung injury and apoptosis were also decreased by Ac2-26 compared to V group. All improvements of Ac2-26 were partly reversed by L-NIO. Conclusions Ac2-26 effectively reduced VILI, improved respiratory function and alveolar-capillary permeability, ameliorated endothelial injury, inhibited oxygen stress and inflammation, and reduced lung injury and apoptosis. Ac2-26-mediated protection of VILI in ARDS rats partly depended on the endothelial nitric oxide synthase pathway.

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.

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