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  • 简介:AIM:Toinvestigatetheneuroprotectiveeffectofgastrodinonretinalganglioncells(RGCs)inanacuteocularhypertension(AOH)ratmodelandtoidentifyitspossiblemechanism.METHODS:AOHratmodelwasperformedinarandomlyselectedeyebyanteriorchamberperfusionandeitherreceivedanintraperitonealinjectionwithvariousconcentrationsofgastrodinornormalsaline.After2wk,theratsweresacrificed.FluoroGoldwasusedtolabelsurvivalRGCs.Immunostainingwithanti-Iba1intheretinalflatmountstocalculatethemicrogliadensityintheganglioncelllayer(GCL).Changesinmicroglialcytokines,tumournecrosisfactor-alpha(TNF-α)andinducibleNOsynthase(iNOS)wereexaminedwithWesternblotandreversetranscriptionquantitativepolymerasechainreaction.Expressionlevelsoftotalandphosphorylatedp38mitogenactivatedproteinkinase(MAPK)weredeterminedbyWesternblot.RESULTS:ResultsshowedthatAOHinducedsignificantlossofRGCsandseveremicrogliaactivationintheGCL.Besides,AOHincreasedthephosphorylationofp38MAPKandpromotedthereleaseofmicroglialcytokinesintheretinas.Intraperitonealinjectionwithdose-dependentgastrodinsignificantlyreducedthelossofRGCsandinhibitedretinalmicrogliaactivation,accompaniedwiththedecreasedexpressionlevelsofmicroglialcytokinesandp38MAPKphosphorylation.CONCLUSION:GastrodinexertsaneuroprotectiveeffectonRGCsinanacuteglaucomaanimalmodelviainhibitingmicrogliaactivationandmicroglial-mediatedneuroinflammation.ThefindingdemonstratesthepotentialapplicationofgastrodinintheneuroprotectivetherapyofacuteglaucomaandotherretinalneurodegenerativediseasescharacterizedbymicrogliaactivationandRGCsdeath.

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