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1、CNVModelinRatsatCBI:在CBI在大鼠角膜新生血管模型HeymannNephritisImmunemediatedFX-1-inducedglomerularnephritisPassiveHeymannnephritisinratsresemblesmembranousnephropathyinman.Itisinducedbyinjectionofsheepantibodytoratproximaltubularepithelialcellbrushborderantigen(anti-Fx1A).Thisis
2、arobustandvalidatedmodelatCBI.Inducewithadministrationofoptimalconcentrationsanti-Fx1AIgGinratsadministeredasasinglesystemicdoseinCFAUrinechanges-markedincreasesinurinaryprotein,creatinineandprotein/creatinineratiosduetoglomerulardamagebeginningwithinoneweekandincreas
3、ingover2-3weeksGlomerularhistologicchangesofglomerularhypercellularity,inflammationanddepositionvisibleby3weekshistologicallyPositivecontrols-notwellunderstood,steroidsnoteffective, mycophenolatemofetilshowsomeactivityHeymannNephritisImmunemediatedFX-1-inducedglomerul
4、arnephritisUrineproteinexcretionincreasesbeginningaboutDay8CharacteristicGlomerularLesionsGlomerularhypercellularitywitheosinophilicdeposition,inflammation,andwirelooplesionsHyperplasiaoftheBowman’scapsuleProteinicmaterialintubulesandtubulardilationInterstitiallympho
5、cyticinflammationATRANSLATIONALAPPROACHTOPRECLINICALRESEARCHHEYMANNNEPHRITISImmunemediatedFX-1-inducedglomerularnephritisHISTOPATHOLOGYLightmicroscopicexaminationStandardstains-HE,Trichrome,SiriusRed,PeriodicacidSchiff,JonesmethenaminesilverstainsImmunohistochemistry-
6、collagen,SMA,basementmembrane,inflammationSemi-quantitativeassessmentOptionforhistomorphometryATRANSLATIONALAPPROACHTOPRECLINICALRESEARCHHEYMANNNEPHRITISImmunemediatedFX-1-inducedglomerularnephritisHISTOPATHOLOGY•AssessmentbyACVPVeterinaryPathologist•Entirekidneyandsu
7、bpartsofthenephronassessed•Glomerulus,mesangium,basementmembrane,Bowman’scapsule,cellularinfiltrates,tubules,interstitium•Incidenceandseverityofthelesionswerescoredusingtheacceptedindustryscoringsystemof0-4,correspondingtonormal,minimal,mild,moderate,andsevere,respect
8、ively.•Lesionsscoredforduration(acute,subacute,andchronic)anddistribution(focal,multifocal,diffuse)basedonthecompositionandn