Pathophysiological Studies of Trinitrobenzene Sulfonic Acid-Induced Colitis in Syrian Hamsters (Mesocricetus auratus)

摘要

WedevelopedacolitismodelinSyrianhamsters(Mesocricetusauratus)toinvestigatetherelationshipbetweencolitisandneutrophilelastase(NE).Colitiswasinducedbyasingleintracolonicdoseoftrinitrobenzenesulfonicacid(TNBS;90mg/ml)dissolvedin15%(vol/vol)ethanol.Theulcerarea,tissuemyeloperoxidase(MPO)activity,andluminalNEactivityallwereincreasedonDays1and5,correspondingwiththeacuteinflammatoryhistopathologicalchanges.TheseacuteinflammatoryparameterssubsequentlydecreasedbyDay14,andchronicinflammatoryhistopathologicalchangesbecameevident.RecurrenceofinflammationwasnotobservedduringtheperioduptoDay28.Toevaluateourcolitismodel,theeffectsofprednisolonewereexamined.Prednisolonewasadministeredorallyonceonthedaybeforeinductionofcolitis,andanimalsweretreatedtwicedailythereafter.AlthoughprednisolonehadlittleeffectonthetissueMPOactivity,prednisoloneinhibitedtheulcerareaandNEactivity.Inaddition,theeffectsofanNE-specificinhibitor(ONO-6818)onourTNBS-inducedcolitismodelwereexamined.Inthesubcutaneoustreatmentstudy,ONO-6818wasadministeredoncebeforetheinductionofcolitis.AlthoughONO-6818hadlittleeffectonthetissueMPOactivity,theulcerareaandNEactivityweredecreasedintheONO-6818-treatedgroup.TheinhibitoryeffectsontheulcerareaandNEactivitywereconfirmedafteroraltreatmentwithONO-6818afterinductionofcolitis.WeconcludethatourcolitismodelisusefulforinvestigatingtherelationshipbetweencolitisandNE,andinhibitionofNEactivitycanpreventtheprogressionofulceration.