Abstract: Objective This study aims to investigate the effect of acteoside on lung injury inrats with severe acute pancreatitis ( SAP ) by regulating the inositol-requiring enzyme 1α(IRE1α) / thioredoxin interacting protein ( TXNIP) / nucleotide binding oligomerization domain-like receptor protein 3 ( NLRP3 ) pathway. MethodsRats were randomly separated into SAPgroup, normal group, acteoside low-dose ( ACT-L ) group, acteoside high-dose ( ACT-H )group, ulinastatin group, ACT-H + empty-vector group, and ACT-H + Ad-IRE1α group, with 12rats in each group. SAP model were constructed by injecting 5 % sodium taurocholate solution into the bile duct of rats. SAP model rats were then administered with acteoside, ulinastatin or AdIRE1α once a day for 2 days. The changes in serum lipase and amylase levels, and lung wet weight / dry weight ratio were detected. HE staining was used to detect the pathological changes of pancreas and lung tissues and to evaluate the pathological scores. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase ( SOD) in lung tissues were detected by kits. ELISA was applied to detect the levels of interleukin-18 and IL-1β in lung tissues. Western blotting was applied to detect the levels of IRE1α, TXNIP, NLRP3, and caspase-1 proteins inlung tissues. Results Pancreatic edema and a large number of cell necrosis and inflammatory cellinfiltration were observed in rats in the SAP group, the inflammatory cell infiltration in lung tissues was observed, and alveolar congestion and alveolar wall edema were severe when compared with those in the normal group. The pancreatic and lung histological scores, the levels of lipase and amylase in serum, the wet / dry lung weight ratio, the levels of MDA, ROS, IL-18, IL-1β in lung tissues, and the expression levels of IRE1α, TXNIP, NLRP3, and caspase-1 proteins were elevated in the SAP group, and the level of SOD in lung tissues was decreased when compared with those inthe normal group (P< 0. 05). The pancreatic and lung tissue damages in rats in the ACT-L group,ACT-H group, and ulinastatin group were improved when compared with those in the SAP group. The pancreatic and lung histological scores, the levels of lipase and amylase in serum, the wet / dry lung weight ratio, the levels of MDA, ROS, IL-18, IL-1β in lung tissues, and the expression levels of IRE1α, TXNIP, NLRP3, and caspase-1 proteins were decreased, and the level of SOD in lung tissues was increased in the ACT-L group, ACT-H group, and ulinastatin groupwhen compared with those in the SAP group (P< 0. 05). The pancreatic and lung tissue damages inthe ACT-H + Ad-IRE1α group were aggravated, and the pancreatic and lung histological scores, the levels of lipase and amylase in serum, the wet / dry lung weight ratio, the levels of MDA, ROS, IL-18, IL-1β in lung tissues, and the expression levels of IRE1α, TXNIP, NLRP3, and caspase-1 proteins were increased, while the level of SOD in lung tissues was decreased when compared withthose in the ACT-H + empty vector group (P< 0. 05). Conclusion The mechanism by which acteoside improves lung injury in SAP rats may be related to the inhibition of IRE1α / TXNIP / NLRP3pathway activation.

Key words: acteoside, inositol-requiring enzyme 1α, thioredoxin interacting protein, nucleotide-binding oligomerization domain-like receptor protein 3, severe acute pancreatitis, lung injury, inflammation, oxidative stress