Enterocyte Shedding and Epithelial Lining Repair Following Ischemia of the Human Small Intestine Attenuate Inflammation 英文参考文献.docVIP

EnterocyteSheddingandEpithelialLiningRepair FollowingIschemiaoftheHumanSmallIntestine AttenuateInflammation RobertA.Matthijsen¤,JoepP.M.Derikx,DianKuipers,RonaldM.vanDam,CornelisH.C.Dejong, WimA.Buurman* DepartmentofSurgery,SchoolforNutritionMetabolism(NUTRIM),MaastrichtUniversityMedicalCenter,Maastricht,theNetherlands Abstract Background: Recently, we observed that small-intestinal ischemia and reperfusion was found to entail a rapid loss of apoptotic and necrotic cells. This study was conducted to investigate whether the observed shedding of ischemically damagedepithelialcellsaffectsIRinducedinflammationinthehumansmallgut. MethodsandFindings:UsinganewlydevelopedIRmodelofthehumansmallintestine,theinflammatoryresponsewas studiedoncellular,proteinandmRNAlevel.Thirtypatientswereconsecutivelyincluded.Partofthejejunumwassubjected to30minutesofischemiaandvariablereperfusionperiods(meanreperfusiontime120(611)minutes).Ethicalapprovaland informed consent were obtained. Increased plasma intestinal fatty acid binding protein (I-FABP) levels indicated loss in epithelial cell integrity in response to ischemia and reperfusion (p,0.001 vs healthy). HIF-1a gene expression doubled (p=0.02) and C3 gene expression increased 4-fold (p=0.01) over the course of IR. Gut barrier failure, assessed as LPS concentrationinsmallbowelvenouseffluentblood,wasnotobserved(p=0.18).Additionally,mRNAexpressionofHO-1,IL- 6, IL-8 did not alter. No increased expression of endothelial adhesion molecules, TNFa release, increased numbers of inflammatorycells(p=0.71)orcomplementactivation,assessedasactivatedC3(p=0.14),weredetectedinthereperfused tissue. Conclusions:Inthehumansmallintestine,thirtyminutesofischemiafollowedbyupto4hoursofreperfusion,doesnot seemtoleadtoanexplicitinflammatoryresponse.Thismaybeexplainedbyauniquemechanismofsheddingofdamaged enterocytes,reportedforthefirsttimebyourgroup. Citation:MatthijsenRA,DerikxJPM,KuipersD,vanDamRM,DejongCHC,etal.(2009)EnterocyteSheddingandEpithelialLiningRep