The role of phosphatidylinositide 3-kinase gamma (P13Kγ) in mediating acinar cell necrosis in rat models with acute pancreatitis / 中华肝胆外科杂志

ABSTRACT

Objective To study the role and mechanism of phosphatidylinositide 3-kinase gamma (P13Kγ) in mediating acinar cell necrosis in rat models with acute pancreatitis.Methods Twelve male C57BL/6 wild-type and twelve male P13Ky knockout mice were randomly divided into saline group and pancreatitis group.The pancreatitis group received an intraperitoneal injection of cerulean (50 μg/kg) to induce acute panreatitis.Pathologic changes in the two groups were observed by measuring the trypsin,cathepsin B,and cathepsin L activity.The protein expressions of cathepsin B and cathepsin L were detected by the Western blot assay.Results Compared with the wild-type mice,the P13Kγγknockout mice had fewer acinar cell necrosis [(2.25± 0.54)/HP vs (5.14±0.85)/HP] and vacuoles [(1.24±0.21)/HP vs (2.36± 0.34)/HP]according to histology.The cathepsin B activity [(1232± 21)pmolAMC/min/mg vs (1891 ±35)pmolAMC/min/mg] and trypsin activity [(0.358± 0.098)pmol/mg vs (0.827± 0.126)pmol/mg] were significantly decreased in the pancreatitis group (P＜0.05) compared to the saline group.However,the cathepsin L activity [ (415 ±11 ) pmolAMC/ min/mg vs (346 ± 6)pmolAMC/min/mg] was significantly higher in P13Kγγ knockout mice than in wild-type mice(P＜0.01).Conclusions P13Kγmay promote cell necrosis in acute pancreatitis by possibly changing the balance between eathepsin B and cathepsin L levels to promote the activation of trypsinogen.