Effect Of Transplantation Of The Bone Mesenchymal Stem Cells On P38MAPK Expression In Pancreas Of Rats With Acute Pancreatitis

ObjectiveAcute pancreatitis (AP) is a potentially life threatening acuteinflammatory condition. The therapeutic options for patients with AP are stilllimited to supportive care because of the pathogenesis of AP have not yet fullyunderstood. In recent years, mesenchymal stem cells is becoming one of thefocus on the treatment in the field of acute pancreatitis because of its successfulapplications in many important diseases. The aim of this study is to investigatethe effect of transplantation of the bone mesenchymal stem cells on p38MAPKexpression in pancreas of rats with acute pancreatitis, and the conceivablemechanism was then deduced.MethodsBone marrow MSCs isolation from femoral and tibial of three tofour-week-old SD rats.The others rats were randomly divided into AP untreatedgroup, MSCs transplanted group, p38MAPK inhibited group and control group.AP was induced in SD rats by2intraperitoneal injections of20%L-arginine hydrochloride at1-hour interval. MSCs (3×106) were transplantatedvia tail, the inhibitor of p38MAPK (SB203580,0.5g/kg) was injectedintraperitoneally1h before injection of L-arginine in transplanted group andinhibited group. The rats were sacrificed1、3、6、12h after the last L-arginineinjection, and blood samples and the pancreas tissue were collected.p38MAPKmRNA expression in the pancreas were measured by RT-PCR,IL-1、IL-17and TNF-α in AP serum were determined by Enzyme-LinkedImmunosorbent Assay, CINC and MCP-1in pancreas tissue were determined byimmunohistochemistry, and pancreas histological changs were observed.ResultsThe level of serum amylase were732.23±265.3U/L、930.55±307.2U/Lat six hour and twelve hour in transplanted group after the last injection ofL-arginine, and at the same timepoints, the level of untreated group were2450.22±466.3U/L、3248.97±365.7U/L. The amylase level of transplantedgroup was significantly lower than that of untreated group (p<0.01).P38MAPKmRNA could be detected in the pancreas with low values incontrol group. Markedly increased and reached the top after L-arginine injected1h in untreated group (p<0.01), but quickly dropped to normal at3h. Althoughp38MAPKmRNA increased slightly in inhibited group and transplanted group,compared with the control group was no significant difference (p>0.05).Pancreatic tissue from the untreated group showed significant mass edemaand inflammation with necrosis compared with the control. When MSCs wereinfused to rats with AP, the edema formation, inflammatory cell infiltration, andnecrosis were reduced significantly in the transplanted group.Immunohistochemistry of pancreas tissue showed that the positive cells of CINC and MCP-1in untreated group were significantly higher than in thetransplanted and the inhibited groups. No significant differences were observedbetween the transplanted and the inhibited groups.ConclusionThe expression of p38MAPKmRNA is increased in the pancreas of APand the damage of the pancreas are aggravated．Transplantation of MSCs couldmarkedly inhibit p38MAPKmRNA expression in the pancreas of AP，whichwould lead to decrease the damage of the pancreas.