Effect of Angiopoietin-Like Protein 4 on Severe Acute Pancreatitis-induced Lung Injury in Rats

Numbers of therapeutic options have been explored for acute pancreatitis (AP), but none has been proven to be effective in clinic. Angiopoietin-like 4 (Angptl4) is a circulating protein, predominantly expressed in the liver and adipose tissue. Overexpression of Angptl4 has been explored in regulating lipid metabolism and angiogenesis. However, Angptl4 is the target gene of preoxisome proliferation activators-PPARs, the latter has been studied with its anti-inflammatory effects. In this study, we investigated effects of Angptl4 on severe acute pancreatitis-induced lung injury in rats. Acute Pancreatitis was induced by retrograde infusion of 1.5% deoxycholic acid sodium salt (1 mg/kg) into the bile-pancreatic duct. The severity of pancreatitis was verified by serum amylase (AMY) and alanine aminotransferase (ALT) levels. BCL-2 expression was observed in pancreatitis tissue performed by immunohistochemistry staining. Pancreatitis-associated lung injury was verified by oxygen saturation (SpO2) levels and pathological changes. Angptl4 and PPAR-γ expression were tested using RT-PCR and Western blotting. The levels of Raf-1 and TNF-α in serum, the expression of vascular endothelial growth factor (VEGF) in lung were also analyzed post operation. The results showed that the Angptl4 level was significantly increased after rosiglitazone (the PPAR-γ agonist) treatment, but there is no difference in GW9662 (PPAR-γ antagonist) group. The roisglitazone treatment significantly alleviated the level of AMY, ALT and TNF-α, and also decreased the expression of VEGF and BCL-2 in the vascular endothelial cells of lung and acinus of pancreas. Our studies indicated that roisglitazone could affect Angptl4 expression and function as a role of anti-inflammatory and antiangiogenic effects.