Early resuscitation with exendin-4 alleviates acute lung injury after hemorrhagic shock in rats.

BACKGROUND: Oxidative stress induced by hemorrhagic shock (HS) is known to initiate a systemic inflammatory response, which leads to subsequent acute lung injury. This study is aimed to assess the efficacy of exendin-4 (Ex-4) in attenuating lung injury in a rat model of HS and resuscitation (HS/R). METHODS: HS was induced in sodium pentobarbital-anesthetized adult male Wistar rats by withdrawing blood to maintain a mean arterial pressure of 30-35 mm Hg for 50 min. Then, the animals received Ex-4 (5 μg/kg) or vehicle (saline) intravenously and were resuscitated with a volume of normal saline 1.5 times that of the shed blood volume. Mean arterial pressure was measured throughout the experiment, and acid-base status, oxidative stress, inflammation, and lung injury were evaluated at 2 h after resuscitation. RESULTS: Ex-4 infusion reduced the methemoglobin content, the malondialdehyde content, the myeloperoxidase activity, and the expression of tumor necrosis factor-α and interleukin-6 in the lungs. The histologic injury was also markedly decreased in the Ex-4 group compared with the vehicle group. CONCLUSIONS: Ex-4 ameliorates the oxidative stress, inflammatory response, and subsequent acute lung injury occurring after HS/R. Although future studies are required to elucidate the underlying mechanism, our results indicate that Ex-4 infusion may be a promising strategy for improving lung injury in the treatment of HS.