| Background In the process of severe acute pancreatitis(SAP),multiple organ will be injury frequently.Pancreas is the first involed organ,with peripancreatic fluid collections and pancreatic tissue necrosis.If not treated in time,local inflammatory reaction will be expanded,leading to systemic inflammatory response and a distant organ injury.Once the intestinal barrier function(IBF)is interrupted,intestinal bacteria and endotoxin will migrate to distant organs,resulting in systemic inflammatory response syndrome(SIRS)and multiple organ dysfunction syndromes(MODS).This is also the main cause of early death in patients with severe acute pancreatitis.For pancreatic injury and intestinal barrier dysfunction treatment,there is no ideal international treatment,so find a new treatment strategy is necessary.Mesenchymal stem cells(MSCs)are adult multipotent stromal cells that can differentiate into specific cell types.The study found that it has a strong immune regulation,anti-inflammatory and tissue repair effect.Studies have shown that bone marrow-derived MSCs transplantation has a very good therapeutic effect on SAP.However,bone marrow-derived MSCs have known disadvantages,including invasive sample collection,limited donor supply and reduced proliferation/differentiation capacity in aging donors,which limit their clinical application.In contrast,human umbilical cord mesenchymal stem cells(ucMSCs)are considered an attractive alternative for clinical applications due to their ready collection,high proliferation and low immunogenicity.At present,ucMSCs has been applied for neurological diseases,diabetes,blood system diseases,but its impact on the treatment of SAP is rarely reported.In our pre-experiment,we found that ucMSCs were distributed in the pancreas and intestinal tissues of the rats with SAP.Based on the above considerations,we systematically investigated the protective effects of ucMSCs on pancreatic and IBF in rats with SAP,which might provide an experimental basis for their clinical application.Part1:Human umbilical cord mesenchymal stem cells alleviate pancreas injury in rats with severe acute pancreatitisPurpose:To observe the effect of umbilical cord mesenchymal stem cells on pancreatic tissue injury in rats with severe acute pancreatitis.Methods:135 male Sprague Dawley rats were randomly assigned to SHAM group(n = 45),SAP group(n = 45)and SAP + ucMSCs group(n = 45).Following intraperitoneal anesthesia with 4% chloral hydrateg,the SHAM group rats received a laparotomy,and the pancreas was turned several times,followed by wound closure.The SAP group:A micro-infusion pump was used for the injection of 5% sodium taurocholate(0.1 ml/100 g)into the pancreatic duct at 12 ml/h.For the SAP+uc MSCs group,the SAP model was first created,and then a tail i.v.injection of CM-Di I-labeled ucMSCs(1×107 cells/kg)was performed..The 72 h mortality of the rats was counted and the rats were sacrificed at 12 h,24h and 72 h after operation.The colonization of the ucMSCs in the pancreas was observed under a fluorescent microscope.Serum amylase,lipase,TNF-?,interleukin-1?(IL-1?),interleukin-4(IL-4),interleukin-10(IL-10)were determined.HE staining was used to observe the changes of pancreatic pathology.The colonization of the uc MSCs in the pancreas was observed under a fluorescent microscope.Results: CM-Dil-labeled ucMSCs were detected in the pancreas of rats with SAP,the pancreatic injury was reduced,serum amylase and lipase were significantly decreased,and systemic inflammation was controlled.Part2:Human umbilical cord mesenchymal stem cells alleviate intestinal barrier injury in rats with severe acute pancreatitisPurpose:To observe the effect of human umbilical cord mesenchymal stem cells on Intestinal barrier function in rates with severe acute pancreatitis.Methods: 45 male Sprague Dawley rats were randomly assigned to SHAM group(n = 15),SAP group(n = 15)and SAP + uc MSCs group(n = 15).The rats in each group were treated with the first part.The rats were sacrificed at 24 h after operation.TNF-?,IL-1?,keratinocyte growth factor(KGF),D-lactate,endotoxin were measured.HE staining was used to observe the pathological changes of small intestine.The pancreas and mesenteric lymph nodes were observed for bacterial culture.The intestinal epithelium was closely connected with microvilli by transmission electron microscopy.The expression of ZO-1 and occludin protein in small intestine was observed by immunofluorescence and western blotting.Results: usMSCs could locate in the injured region of the small intestine.us MSC transplantation also significantly lowered the levels of the inflammatory factors tumor necrosis factor-? and interleukin-1? and of the pathological score of the small intestine.Importantly,us MSC transplantation increased the expression of intestinal keratinocyte growth factor and improved the intestinal barrier function,as evidenced by the decrease in D-lactate,endotoxins and bacterial migration and the increase in tight junction proteins zona occludens 1 and occludin expression.Conclusion:1.ucMSCs transplantation can be homing to SAP rats pancreas and intestinal tissue2.ucMSCs transplantation significantly reduced the levels of trypsin and lipase in rats with SAP,reduced pancreatic injury,and inhibited systemic inflammatory response3.ucMSCs transplantation significantly reduced the level of small intestinal inflammatory factors in rats with SAP,up-regulated the expression of KGF in the small intestine and improved the intestinal barrier function... |
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