Bone marrow-derived mesenchymal stem cells ameliorate severe acute pancreatitis by inhibiting oxidative stress in rats

Abstract

To investigate whether bone marrow mesenchymal stem cells (BMSCs) attenuate pancreatic injury via mediating oxidative stress in severe acute pancreatitis (SAP). The SAP model was established in rats. Phosphate buffered saline (PBS) or BMSCs were injected into the rats by tail veins. ML385 was used to down-regulate Nrf2 expression in rats. Pancreatic pathological score was used to evaluated pancreatic injury. Inflammatory-associated cytokines, serum lipase and amylase, levels of myeloperoxidase, malondialdehyde, reactive oxygen species and superoxide dismutase, as well as catalase activity were measured for injury severity evaluation. ML385 aggravates oxidative stress in SAP + ML385 group, compared with SAP + PBS group. BMSCs transplantation alleviated pancreatic injury and enhance antioxidant tolerance in SAP + BMSCs group, while ML385 administration weakened this efficacy in SAP + BMSCs + ML385 group. In addition, BMSCs promoted Nrf2 nuclear translocation via PI3K/AKT signaling pathway. Besides, BMSCs reduced inflammatory response by inhibiting NF-κB signaling pathway in SAP. BMSCs can inhibit oxidative stress and reduce pancreatic injury via inducing Nrf2 nuclear translocation in SAP.