Abstract: Abstract： Objective To investigate the optimal dose of apocynin to protect severe acute pancreatitis (SAP) and SAP caused intestinal injury in rats. Methods A total of 53 SPF male Wistar rats were randomly allocated into five groups: sham operation group (SO group, n=10), SAP group (n=12), low-dose apocynin group (25 mg/kg， n=11), medium-dose apocynin group (50 mg/kg， n=10) and high-dose apocynin group (100 mg/kg， n=10). SAP model was prepared by retrograde infusing 5% sodium taurocholate (1 mL/kg) into biliopancreatic duct of rat. At thirty minutes before modeling, apocynin was injected into rat to intervention. The survival condition was recorded at 12 h after modeling, and blood samples were obtained for detecting serum amylase (AMY), alanine aminotransferase (ALT) and creatinine (Cr). Pancreatic and ileal tissue samples were obtained for HE staining and pathological examination. Results Two rats died in SAP group and one died in low-dose apocynin group. The quantity of ascites, the levels of AMY, ALT, Cr and pancreatic and intestinal pathologic scores were significantly increased in SAP group than those in SO group (P < 0.05). Except the levels of Cr and intestinal pathologic score, there was no significant difference between low- dose apocynin group and SAP group. The quantity of ascites ascites, levels of AMY, Cr and pancreatic and intestinal pathologic scores were significantly lower in medium-dose and high-dose apocynin groups than those in SAP group (P < 0.05). The levels of ALT and Cr were significantly higher in high-dose apocynin group than those of medium-dose apocynin group (P < 0.05). Conclusion Apocynin improves SAP symptoms and reduces SAP caused intestinal injury in rats, which may be related to the inhibition of NOX activity, and 50 mg/kg of apocynin is the optimal dose.

Key words:  pancreatitis, acute necrotizing, apocynin, severe acute pancreatitis, NOX, ascites,  intestinal injury, dose- response relationship, drug