EGFL7抑制Sestrin2/Nrf2信号通路促进血管生成加剧大鼠糖尿病视网膜病变OA

Objective To investigate the impact of epidermal growth factor-like domain 7(EGFL7)on angiogenesis in diabetic retinopathy,based on the Sestrin2/nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway.Methods A diabetic retinopathy model was established in the rats.Retinal pathological morphology was examined using hematoxylin-eosin(HE)staining,while retinal vascular morphology was assessed via the retinal trypsin digestion assay.The mRNA expression levels of EGFL7,Sestrin2,Nrf2,and heme oxygenase-1(HO-1)in retinal tissues were analyzed by RT-qPCR.Protein expression levels of EGFL7,Sestrin2,cluster of differentiation 31(CD31),vascular endothelial growth factor receptor 2(VEGFR2),Nrf2,and HO-1 w ere detected by Western blot.Corresponding assay kits were used to measure the levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in the intraocular aqueous humor.Results Compared with the control group,rats in the model group exhibited pathological damage in retinal tissues,increased retinal vascular density,and elevated levels of EGFL7,CD31,VEGFR2,and MDA(P<0.05),whereas levels of SOD,GSH-Px,Sestrin2,Nrf2,and HO-1 were decreased(P<0.05).No significant changes were observed in the above pathological indicators in the IgG group compared with the model group(P>0.05).In contrast,compared with the IgG group,rats in the anti-EGFL7 group showed alleviated retinal pathological injury,reduced retinal vascular density,decreased levels of EGFL7,CD31,VEGFR2,and MDA(P<0.05),and increased levels of SOD,GSH-Px,Sestrin2,Nrf2,and HO-1(P<0.05).Conclusion EGFL7 may exacerbate retinal neovascularization in diabetic retinopathy rats by promoting oxidative stress,a mechanism potentially associated with the inhibition of the Sestrin2/Nrf2 signaling pathway.