Resveratrol Improves The Therapeutic Efficacy Of Bone Marrow-derived Mesenchymal Stem Cells In Rats With Severe Acute Pancreatitis

Objective: Bone marrow-derived mesenchymal stem cells(BMSCs)are effective in the treatment of severe acute pancreatitis(SAP),but their therapeutic effects could still be improved.In order to optimize the clinical application of BMSCs,we adopted the strategy of resveratrol(Res)pretreatment of BMSCs(Res-BMSCs)and applied it to a rat model of sodium taurocholate(Na T)-induced acute pancreatitis.To observe whether resveratrol pretreatment of BMSCs can enhance the therapeutic effect of BMSCs on SAP.Methods: SAP was induced by injection of 3% Na T into the pancreatic duct and successful induction of SAP occurred after 12 h.SD rats were divided into 7 groups:normal control group,pancreatitis group,vandetanib group,resveratrol group,stem cell treatment group,stem cell pretreatment group,pretreatment combined with vandetanib group.stem cells group and their pretreatment group were given resveratrol pretreatment and untreated BMSCs treatment,resveratrol group was given resveratrol(Res)treatment,Res concentration was 40mmol/L,the vandetanib(ZD6474)group was given 50 mg / kg daily gavage treatment,the pancreatitis group was not treated.Results: The treatment effect of stem cell pretreatment group was the most obvious,after the treatment,the levels of lipase,amylase and pro-inflammatory factors in rats decreased significantly,and the pro-apoptotic proteins Bax,cleaved caspase 3 and cleaved Caspase-9 expression were decreased,angiogenesis related protein CD31,VEGFA,VEGFR2 expression increased,PI3K/Akt signal pathway,which is an important pathway of anti-apoptosis and angiogenesis was increased.But its therapeutic effect will be significantly weakened by vandetanib,Conclusion: Resveratrol-preprocessed BMSCs can activate the PI3K/AKT signaling pathway in pancreatic cells and HUVECs through paracrine release of VEGFA;thus,achieving the therapeutic effect of resisting apoptosis of pancreatic cells and promoting regeneration of damaged blood vessels.Res pretreatment may be a new strategy to improve the therapeutic effect of BMSCs on SAP.