PossiblemechanismofIGF-1Rinhibitorinhibitingrenalfibrosisinmicewithdiabeticnephropathy

Abstract:

Objective：Toinvestigatethepossiblemechanismofinsulin-likegrowthfactor1receptor（IGF-1R）inhibitorinhibitingrenalfibrosisinmicewithdiabeticnephropathy.Methods：Ninety8-week-oldC57/BL6maleratswereequallyandrandomlydividedintofivegroups：groupA（diabeticnephropathygroup），groupB（IGF-1Rgroup），groupC（angiotensin-converting-enzymeinhibitorgroup），groupD（insulingroup），andcontrolgroup.GroupsA-Dwereintraperitoneallyinjectedwith100mg/kgstreptozotocintoestablishadiabetesmodel，whichwasconfirmedwith48hrandombloodglucose（≥16.7mmol/L）andurineglucose（+~4+）.After8weeksofmodeling，groupAwasgivennormalsalinebygavage，groupBwasgiven30mg/kgIGF-1Rinhibitorbygavageonceevery48h，groupCwasgiven30mg/kgangiotensin-converting-enzymeinhibitoronceevery48h，andgroupDwasinjectedsubcutaneouslywith1-2U/kginsulin.Theurinecreatinine，bloodglucose，and24-hourproteinexcretionineachgroupwereroutinelytested.Attheageof16weeks，themiceineachgroupwereanesthetizedandsacrificed.Therenaltissuesampleswerecollectedandroutinelyparaffin-embeddedforhistopathologicalexamination.Results：Thebloodglucoseinthecontrolgroupwasnormal.ThebloodglucoselevelsingroupsA-Cwerehigherthan16.7mmol/L，andthatingroupDwaslowerthan16.7mmol/L.Therewasasignificantdifferenceinbloodglucosebetweenthegroups（P<0.05）.Theurinarypro－teinexcretionrateingroupAwassignificantlyhigherthanthatinthecontrolgroup（P<0.05）；theurinaryproteinexcretionratesingroupBandDweresignificantlylowerthanthatingroupA（P<0.05）.Theurinaryprotein/creatinineratioingroupAwassignificantlyhigherthanthatinthecontrolgroup（P<0.05）；comparedwithgroupA，groupsBandDhadasignificantlylowerurineprotein/creatinineratio（bothP<0.05）.InsituhybridizationassayshowedthattheexpressionofSnail1andIGF-1intherenaltissuewasup-regulatedinmicewithdiabeticnephropathy.Comparedwiththecontrolgroup，groupAhadnosignificantchangeinthemRNAexpressionofIGF-1（P>0.05），buthadsignificantlylowermRNAexpressionofSnail1（P<0.05）；nosignificantchangesinthemRNAexpressionofSnail1andIGF-1intherenaltissuewereobservedingroupsCandD（P>0.05）.Immunohistochemicalstainingresultsshowedthatcomparedwiththecontrolgroup，groupAhadsignifi－cantlyhigherproteinexpressionofSnail1andIGF-1intherenaltissue（P<0.05）；groupBhadnosignificantchangeintheproteinexpressionofIGF-1（P>0.05），buthadsignificantlylowerproteinexpressionofSnail1（P<0.05）.NosignificantchangesintheproteinexpressionofSnail1andIGF-1wereobservedingroupsCandDcomparedwithgroupA（P>0.05）.Conclusion：InhibitingIGF-1RorsilencingIGF-1caninhibitrenaltubularepithelial-mesenchymaltransitionandrelieverenalfibrosis.