No abstract

The main causes of lung injury after cardiopulmonary bypass (CPB) are systemic inflammatory response syndrome (SIRS) and pulmonary ischaemia‐reperfusion injury (IR‐I). SIRS and IR‐I are often initiated by a systemic inflammatory response. The present study investigated whether the annexin A1 (ANX‐A1) peptidomimetic Ac2‐26 by binding to formyl peptide receptors (FPRs) inhibit inflammatory cytokines and reduce lung injury after CPB. Male rats were randomized to the following five groups (n = 6, each): sham, exposed to pulmonary ischaemic‐reperfusion (IR‐I), IR‐I plus Ac2‐26, IR‐I plus the FPR antagonist, BoC2 (N‐tert‐butyloxycarbonyl‐Phe‐Leu‐Phe‐Leu‐Phe) and IR‐I plus Ac2‐26 and BoC2. Treatment with Ac2‐26 improved the oxygenation index, an effect blocked by BoC2. Histopathological analysis of the lung tissue revealed that the degree of lung injury was significantly less (P < 0.05) in the Ac2‐26‐treated rats compared to the other experimental groups exposed to IR‐I. Ac2‐26 treatment reduced the levels of the inflammatory cytokines TNF‐α, IL‐1β, ICAM‐1 and NF‐κB‐p65 (P < 0.05) compared to the vehicle‐treated group exposed to IR‐I. In conclusion, the annexin A1 (ANX‐A1) peptidomimetic Ac2‐26 by binding to formyl peptide receptors inhibit inflammatory cytokines and reduce ischaemic‐reperfusion lung injury after cardiopulmonary bypass.

Acute exposure to hydrogen sulfide (H 2 S) can cause fatal acute lung injury (ALI). However, the mechanisms of H 2 S-induced ALI are still not fully understood. This study aims to investigate the role of the tight junction protein claudin-5 in H 2 S-induced ALI. In our study, Sprague-Dawley (SD) rats were exposed to H 2 S to establish the ALI model, and in parallel, human pulmonary microvascular endothelial cells (HPMECs) were incubated with NaHS (a H 2 S donor) to establish a cell model. Lung immunohistochemistry and electron microscopy assays were used to identify H 2 S-induced ALI, and the expression of claudin-5, p-AKT/t-AKT and p-FoxO1/t-FoxO1 was detected. Our results show that H 2 S promoted the formation of ALI by morphological investigation and decreased claudin-5 expression. Dexamethasone (Dex) could partly attenuate NaHS-mediated claudin-5 downregulation, and the protective effects of Dex could be partially blocked by LY294002, a PI3K/AKT/FoxO1 pathway antagonist. Moreover, as a consequence of the altered phosphorylation of AKT and FoxO1, a change in claudin-5 with the same trend was observed. Therefore, the tight junction protein claudin-5 might be considered a therapeutic target for the treatment of ALI induced by H 2 S and other hazardous gases.

No abstract

No abstract