Protective Effects Of Mesenchymal Stem Cells On Intestinal Barrier In Rats Model With Severe Acute Pancreatitis

[Objective]To investigate the protective effect of MSCs on intestine barrier functional disturbance induced by severe aeute pancreatitis(SAP) and its possible mechanism.[Methods]There were Fifty-four Male Sprague-Dawley (SD)rats weighing(250-350g, They were randomly divided into three equal groups:sham operation(SO) group, SAP group and SAP+MSCs treatment group.Rats of SAP were induced by retrograde injection of4%sodium tatiroeholate into the biliopancreatic duct. SAP+MSCs treatment groups were given penis dorsal vein administrated MSCs at a dosage of1*106/100g. There were four time piongs for every group(namely at6、12、24、48h).Rats in each group were killed after observed at6、12、24、48h and the serum levels of AMY、TNF-α DAO in the intestinal mueosa were examined respectively at6、12、24、48hours after operation for each group.The MSCs of passage3were stained with Chlormethylbenzamido-1,1dioctadecyl-3,3,3’,3’-tetramethylin docarbocyamine (CM-DiI) and observed CM-DiI positive cells with fluorescent microscope. Intestinal tissue organization of AQP-1protein expression was evaluated and intestinal tissue and pancreastissue were further pathologied and changes in patbology were also observed.[Results]l.The serum levels of AMY、TNF-α、 DAO in the SAP group at differenit four time piongs were all signifieantly higher than those in the sham operation(SO) group.As compared with SAP group, the contents of TNF-α was significantly decreased in SAP+MSCs group at all the4time points (P<0.05). while the level of DAO significantly decreased in SAP+MSCs group except for the12、24h (P<0.05).2. There were signifieanily different about the histological injury degree of pancreatitis and intestine barrier functional disturbance at the different four time piongs with increasing of serum levels of DAO, pathologieal changes of pancreas and intestine were aggravating.The pathological scores of the small intestine and panereas at the different time points were rising.But after treatment with MSCs, the changes became lower than those in SAP group.CM-DiI positive cells could be seen at intestinal tissue of SAP+MSCs group rats with fluorescent microscope. Immunohistochemical results show that positive expression of AQP-1in SAP group weaker than SO group after6h, especially in the24hours, but positive expression of AQP-1in SAP+MSCs group after12h, has been enhances compared with SAP group.[Conclusions]1. Rats of SAP were induced by retrograde injection of4%sodium tatiroeholate into the biliopancreatic duct, this experimental method is stable and repeatable.2. Adherent culture of bone marrow can gain highly purified MSCs.3.Severe acute pancreatitis could lead to systemic inflammation response in rats, transplanted MSCs could transfer to and settle at injuried small intestine tissue, inhibition of inflammatory mediators release, incresed expression of AQP-1, reduce intestinal permeability, promotion of intestinal epithelial repair, maintain the integrity of the intestinal mucosal barrier.