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1、Br.J.exp.Path.(1983)64,425EXPERIMENTALINTERSTITIALRENALFIBROSISINRATS:NEPHRITISINDUCEDBYN-(3,5-DICHLOROPHENYL)SUCCINIMIDEM.C.BARRETT,S.J.CASHMAN*ANDJ.MOSSFromtheDepartmentofHistopathologyandExperimentalPathology,CharingCrosmHospitalMedicalSchool,FulhamPalaceRoad,LondonW68RFRe
2、ceivedforpublicationFebruary25,1983Summary.-ThenephrotoxicpropertiesofthechemicalN-(3,5-dichlorophenyl)-succinimidewereinvestigatedinratswithaviewtoestablishingtheusefulnessofthischemically-inducednephritisasamodelofchronicinterstitialrenalfibrosis.Thecompoundwassynthesizedan
3、dgivendailybygastricintubationasasuspensioninarachisoilB.P.tomaleWAG-strainrats,forperiodsofupto108days.Polydipsiaandpolyuriaresultedrapidlyinalltreatedanimalsandpersistedforthedurationoftheexperiment.Therewasaprogressiveincreaseintheextentofproteinuriainalltreatedanimalsand,
4、bytheendoftheexperiment,therewasanincreaseintheplasmalevelsofureaandcreatinine.Shorttermtreatment(upto3days)resultedinfocalareasofnecrosisofsomeproximalconvolutedtubules.Treatmentfor28daysresultedinpatchybutseveretubularinterstitialnephritiswithwhichwasassociatedamoderateinte
5、rstitialfibrosis.By108days,thenephritiswasmorewidespreadandtheinterstitialfibrosiswassevere.Theactivityofprolinehydroxylase,apartoftheintracellularsequenceofcollagensynthesis,showedprogressiveincreaseintherenalcortexthroughouttheexperimentandtherewasanassociatedincreaseinthec
6、orticalhydroxyprolinecontent,ameasureoftheamountofcollagenpresent.Associatedwiththisbiochemicalevidenceofanactive,chronicfibrosis,wasanincreasedwatercontentofthecorticaltissue.Theresultsindicatethatthischemically-induced,tubularinterstitialnephritisisindeedagoodandreliablemod
7、elofinterstitialrenalfibrosis.INRECENTYEARSithasbecomeapparentcollagenformationwemightbeabletothatthediminutionofrenalfunctionseenimproverenalfunction.invariousformsofglomerularnephritisTotestthispossibility,wefirstneededisassociatedasmuchwithatrophyoftheareadilyreproduciblee
8、xperimentalmodelrenaltubulesandfibrosisoftheinter-ofrenalfibrosis.Tw
