Protective effect of nimesulide on acute lung injury in mice with severe acute pancreatitis

The study was designed to investigate the effect of Nimesulide (NIM) on acute lung injury (ALI) in mice with severe acute pancreatitis (SAP). In our study, caerulein and LPS were employed to establish the ALI mice model induced by SAP. All animals were divided into four groups randomly: control, model (SAP), NIM low and high dosages groups. Following treatment with NIM, histopathology observation of pancreatic tissues and lung tissues were detected by hematoxylin and eosin (H&E) staining. The levels of serum amylase, lipase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta and IL-6 were measured by ELISA. The ratio of wet lung to dry lung (W/D) was calculated. In addition, the expression levels of TNF-alpha, IL-1 beta and IL-6 were measured by Western blotting. Moreover, the expression of cyclooxygenase 2 (COX 2) was detected using Immunohistochemistry analysis. The results revealed that NIM markedly improved pancreatic histological injury and decreased the levels of serum amylase, lipase, TNF-alpha, IL-1 beta and IL-6 in a dose-dependent after NIM treatment. For ALI induced by SAP, pulmonary edema were significantly alleviated compared with the mice in SAP group. In addition, the decreased ratio of W/D were observed after NIM intervene. The expression levels of TNF-alpha, IL-1 beta and IL-6 proteins were downregulated following NIM treatment. More, NIM inhibited the expression of COX2 in lung tissues. Taken together, our study demonstrated that NIM was able to protect against ALI induced by SAP via inhibiting inflammation, which will be of novel therapeutic strategies for the clinical treatment of ALI.