AIM:To explore the role of Pioglitazone(Pio) on a mouse model of retinal ischemia/reperfusion(I/R) injury and to elucidate the potential mechanism.METHODS:Retinal ischemia was induced in mice by increasing the i...AIM:To explore the role of Pioglitazone(Pio) on a mouse model of retinal ischemia/reperfusion(I/R) injury and to elucidate the potential mechanism.METHODS:Retinal ischemia was induced in mice by increasing the intraocular pressure,and Pio was administered 4 h though periocular injection before I/R.The number of cells in the ganglion cell layer(GCL) was counted 7 d after retinal I/R injury.Glial fibrillary acidic protein(GFAP),nuclear factor-kappa B(NF-κB),p38,phosphorylated-p38,PPAR-γ,interleukin-1β(IL-1β),Toll-like receptor 4(TLR4),NLRP3,cleaved caspase-1,caspase-1 were determined by real-time polymerase chain reaction and Western blotting.RESULTS:Pio promoted the survival of retinal cells in GCL following retinal I/R injury(P〈0.05).Besides,retinal I/R injury stimulated the expression of GFAP and TLR4,which were partially reversed by Pio treatment(P0.05).Retinal I/R injury-upregulated expression of NLRP3,cleaved caspase-1,IL-1β was attenuated after Pio treatment(P〈0.05).Moreover,I/R injury induced activation of NF-κB and p38 were inhibited by Pio treatment(P〈0.05).CONCLUSION:Pio promotes retinal ganglion cells survival by suppressing I/R-induced activation of TLR4/NLRP3 inflammasomes via inhibiting NF-κB and p38 phosphorylation.展开更多
基金Supported by National Natural Science Foundation of China(No.81300777)the General Program of Shanghai Municipal Health and Family Planning Commission(No.201440522)
文摘AIM:To explore the role of Pioglitazone(Pio) on a mouse model of retinal ischemia/reperfusion(I/R) injury and to elucidate the potential mechanism.METHODS:Retinal ischemia was induced in mice by increasing the intraocular pressure,and Pio was administered 4 h though periocular injection before I/R.The number of cells in the ganglion cell layer(GCL) was counted 7 d after retinal I/R injury.Glial fibrillary acidic protein(GFAP),nuclear factor-kappa B(NF-κB),p38,phosphorylated-p38,PPAR-γ,interleukin-1β(IL-1β),Toll-like receptor 4(TLR4),NLRP3,cleaved caspase-1,caspase-1 were determined by real-time polymerase chain reaction and Western blotting.RESULTS:Pio promoted the survival of retinal cells in GCL following retinal I/R injury(P〈0.05).Besides,retinal I/R injury stimulated the expression of GFAP and TLR4,which were partially reversed by Pio treatment(P0.05).Retinal I/R injury-upregulated expression of NLRP3,cleaved caspase-1,IL-1β was attenuated after Pio treatment(P〈0.05).Moreover,I/R injury induced activation of NF-κB and p38 were inhibited by Pio treatment(P〈0.05).CONCLUSION:Pio promotes retinal ganglion cells survival by suppressing I/R-induced activation of TLR4/NLRP3 inflammasomes via inhibiting NF-κB and p38 phosphorylation.