二精丸改善糖尿病视网膜神经变性的机制研究OA

Objective To investigate the mechanism by which Erjing Pill(二精丸,EJP)ameliorates diabetic retinal neurodegenera-tion(DRN)by activating moderate autophagy in Müller cells and regulating the AGEs/RAGE-Nrf2/HO-1 signaling pathway.Methods Streptozotocin-induced diabetic rat models were established and randomly divided into control group(CON),model group(MOD),cal-cium dobesilate group(CDC),and low/high-dose EJP groups(PL-L/H).After 12 weeks of intervention,ELISA was used to detect serum oxidative stress indices(SOD,MDA,GSH,CAT),GLU,retinal inflammatory cytokines(TNF-α,IL-6,IL-1β),and the con-tents of thioredoxin-interacting protein(TXNIP)and microtubule-associated protein LC3-Ⅱ in vitreous humor.Immunofluorescence(IF)was performed to detect the expression of caspase-3 and deposition of AGEs in retinal tissues.Western blot(WB)was used to mea-sure the protein levels of TXNIP,LC3-Ⅱ,Caspase-3,RAGE,and NF-κB in retinal tissues.RT-qPCR was employed to analyze the relative mRNA expression of RAGE,Nrf2,and HO-1 in retinal tissues.Key molecules involved in apoptosis,antioxidation,and autophagy regulation were analyzed.Results Following EJP intervention,the PL-H group exhibited significant upregulation of SOD,CAT,and GSH levels,alongside reduced levels of MDA,GLU,TNF-α,IL-6,IL-1β,RAGE,NF-κB,TXNIP,caspase-3,and LC3-Ⅱ.IF staining showed decreased fluorescence intensity of AGEs and caspase-3.TXNIP and LC3-Ⅱ levels in vitreous humor were also reduced.The relative mRNA expression of Nrf2 and HO-1 in retinal tissues showed an upward trend,while that of RAGE showed a downward trend.Conclusion EJP ameliorates DRN through a dual mechanism:regulating autophagic flux in Müller cells to alleviate glu-tamate excitotoxicity;inhibiting the AGEs/RAGE-mediated NF-κB inflammatory cascade and activating the Nrf2/HO-1 antioxidant defense system.