| Objective:Severe acute pancreatitis(SAP) is a commom severe acuteabdomen in clinical. dysfunction.It ranks14th among gastrointestinal andliver diseases that can cause death. Pancreatic injury is often associated withother organs’dysfunction.Numerous studies have confirmed that the pathologychanges mediated by intestinal mucosal barrier injury due to severe acutepancreatitis plays a key role in its pathogenesis. The function of immunebarrier in the intestinl mucosal barrier can not be ignored.It is an importantbranch of the body’s entire immune system, maintaining normal intestinalimmune response.The damage of the intestinal mucosal immune barriercaused by SAP will cause a decline in the intestinal immune function.Intestinal bacteria and toxins will increase and cause microfloradisorders,therefore the intestinal infection will increase.What’s more,epithelialcell renewal and repairment slow down, digestion and absorption function areimpaired, so nutrients are reduced.The disease will deteriorate. Under thepremise of increased intestinal permeability, bacterial endotoxin causes asecondary infection of the pancreas,which may stimulate systemicinflammatory response syndrome (SIRS) and multiple organ dysfunctionsyndrome (MODS). Therefore, while we attach importance to the treatment ofthe primary disease, the protection of intestinal mucosal barrier is also veryimportant. In the recent years,mannose has been found to be an effectiveanti-inflammatory substances found in animal experiments.It has manyfunctions such as antioxidation, anti-inflammatory medium and protection oforgans. In this study, in order to observe the effect of mannose on intestinalmucosal immune barrier,we established the model of severe pancreatitis, andmannose was applied in the treatment group. Methods:1Experimental animal groups:60adult male SD rats ofpathogen-free were randomly divided into sham operation (A) group,pancreatitis (B) group and mannose treatment (C) group.Each group wasdivided into two subgroups according to time points,6hour group and12hour group,so there are10rats in each of the6subgroups. The severe acutepancreatits group was retrogradely injection of5%sodium taurocholate afterpuncturing into the duodenal pancreatic bile duct.The treatment group wasimmediately injected with0.3g/kg mannose via the tail vein after the successof the model is established in5minutes and finally the abdominal wall wassutured. The sham group only was performed laparotomy and flippedduodenum,then the abdominal wall was sutured.Blood, pancreas, intestinaltissue and intestinal mucus were collected after the6hour and12hour.2Experimental methods:we observed pancreas and intestinal histopathol-ogy with optical microscope, ELISA was used to detect the concentration ofserum mannose binding lectin (MBL) and intestinal tissue homogenates IL-4,separated intestinal intraepithelial lymphocytes was evaluate by flowcytometry, we labeled mucosal lamina propria CD4and CD8T lymphocyteswith immunohistochemistry methods to evaluate the expression,radio-immun-oassay was used to detects intestinal mucus slgA level.3Statistical Methods: we used SPSS16.0for windows to performstatistical analysis.All datas were presented as mean±SD. Homogeneity ofvariance and normality were tested, and then the appropriate statisticalmethods were applied. Two-tailed tests of significance were used andsignificance was assumed at P<0.05.Results:1Histopathological changes of pancreatic tissue:in the sham-operated group(A6, A12): the structure of the pancreatic tissue was intact, andthe acinar lobule and glands were clearly visible, no bleeding or necrosis.The-re was no difference between the two time points. Model group(B6,B12):Pancreatic interlobular septum was highly swallen, and acinar cellsformed vacuoles.There was extensive infiltration of inflammatory cells in thelobules and visible necrosis and hemorrhage. The above changes were morecommon in12hour group than that in6hour group. Treatment group (C6,C12):There was obvious inflammatory changes. Hemorrhage and necrosisof the pancreas was mild alleviated compared with the model group.There wasno significant difference between the two time points in the teratment group.2Histopathological changes of Intestine:the sham-operated group (A6,B6):Intestinal mucosal villis were of neatly arranged.The intestinal epithelial celllayer was intact, and the brush border was smooth with a thin layer of mucus.There was not obvious inflammation. No difference existed between the twotime points. Model group(B6,B12):Intestinal epithelial cells degenerated andnecrosed, some epithelial cells sheded exposing the lamina propria. Thearrangement of villus was disordered and some villus sheded. There were alarge number of infiltrated neutrophil cells,telangiectasia, and congestion inthe lamina propria. The above changes was more common in12hour groupthan that in6hour group.Treatment group(C6,C12):The degree of intestinalinflammatory damage reduced compared with the model group.There was nosignificant difference between the two time points.3The changes of serum MBL level:compared with the same time pointin the sham-operated group, serum MBL level significantly increased inmodel group and treatment group(P<0.05); Compared with the same timepoint in model group,serum MBL level significantly increased in the treatmentgroup(P<0.05);Comparison between the subgroups in the treatment groupshowed that serum MBL level growed with the time.(P<0.05);Comparisonsbetween the subgroups in the sham-operated group and model group showedthat there was no significant difference between the two time points(P>0.05).4The changes of intestinal mucus sIgA level:compared with the sametime point in the sham-operated group, intestinal mucus sIgA levelsignificantly decreased in the model group and treatment group (P<0.05);Compared with the same time point in model group, intestinal mucus sIgAlevel increased in the treatment group(P<0.05); Comparisons of the subgroupsin the same group showed that there was no significant difference between thetwo time points(P>0.05).5The changes of intestinal tissue homogenates IL-4level: compared with the same time point in the sham-operated group, the intestinal tissuehomogenates IL-4level significantly reduced in the model group andtreatment group (P<0.05); Compared with the same time point in model group,intestinal tissue homogenates IL-4level significantly increased in thetreatment group in12hour group(P<0.05),but there was no significantdifference in6hour group(P>0.05); Comparison between different time pointin the treatment group showed that its level was higher in12hour group thanthat in6hour group(P<0.05); Comparisons of the subgroups in thesham-operated group and model group showed that there was no significantdifference between the two time points(P>0.05).6The changes of intestinal epithelial lymphocytes: compared with thesame time point in the sham-operated group, CD3and CD4T lymphocytes ofintestinal intraepithelial lymphocytes had a significant reduction,CD8Tlymphocytes did not change significantly in the model group and thetreatment group(P<0.05);Compared with the same time point in modelgroup,CD3and CD4T lymphocytes of IELs significantly increased (P<0.05),CD8T lymphocytes did not change significantly in the treatmentgroup(P<0.05); Comparisons between the subgroups within the same groupshowed that there was no significant difference between the two timepoints(P>0.05).7The changes of intestinal lamina propria lymphocytes: compared withthe same time point in the sham-operated group, CD4、CD8T lymphocytes didnot change significantly in6hour group of the model group and the treatmentgroup, CD4、CD8T lymphocytes decreased significantly in12hour group ofthe model group and the treatment group(P<0.05); Compared with the sametime point in the model group, CD4、CD8T lymphocytes did not changesignificantly in6hour group，but significantly increased in12hour group inthe treatment group(P<0.05); Comparisons between the different time pointsin the model group showed that CD4、CD8T lymphocytes significantlydecreased in12hour group(P<0.05); Comparisons between the different timepoints of the treatment group showed that CD4、 CD8T lymphocytes significantly decresed in12hour group(P<0.05); Comparisons between thedifferent time points in the sham-operated group showed that no significantdifference in CD4、CD8T lymphocytes(P>0.05).Conclusion:1Severe acute pancreatitis not only cause pancreatic injurybut also lead to the damage of the intestinal mucosal immune barrier. Thedamage is aggravating with the time. The damage is manifested by reducingthe secretion of sIgA and IL-4,and the number of IEL and LPL.2Mannose has a protective effect on intestinal mucosal immune barrierin rats with severe acute pancreatitis.3Mannose can increase the level of the MBL, and enhance the body’sresistance.4The protective mechanism of mannose may be that it stimulates theliver to secrete more MBL,and increase the level of the intestinal sIgA and IL-4,and increase the number of IEL and LPL.There may also be some othermechanisms.Further validation is still in need. |
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