大豆异黄酮对激素性青光眼RGCs的保护作用研究OA

·AIM:To investigate the neuroprotective effects of soy isoflavones(SI)against glucocorticoid-induced retinal ganglion cells(RGCs)injury in a rat model of acute ocular hypertension(AOH),and to explore the underlying mechanism involving the PI3K/Akt/Caspase-3 signaling pathway. ·METHODS:A total of 48 Sprague-Dawley(SD)rats(48 eyes)were randomly assigned to four groups(n=12 per group):a control group(received normal saline),an AOH control group,a low-dose SI intervention group[LSI+AOH,360 mg/(kg·d)],and a high-dose SI intervention group[HSI+AOH,540 mg/(kg·d)].The AOH,LSI+AOH,and HSI+AOH groups received subconjunctival injections of dexamethasone to induce AOH control group.From the 3 wk of modelling,SI was administered via intraperitoneal injection until 4 wk.Intraocular pressure(IOP)was monitored,RGC density was assessed,and the protein expression levels of PI3K/phosphorylated Akt(p-Akt)/Caspase-3,and key inflammatory cytokines were evaluated. ·RESULTS:IOP was significantly higher in the AOH control group compared to the control group(P<0.01).Both the LSI+AOH and HSI+AOH groups exhibited a marked reduction in IOP compared to the AOH control group(all P<0.01).RGC density was significantly lower in the AOH control group than in the control group(P<0.01),but was notably increased in the LSI+AOH group and the HSI+AOH group compared with the AOH control group(all P<0.01).Compared with the control group,the AOH control group demonstrated downregulated protein expression of PI3K and p-Akt,alongside upregulated expression of activated Caspase-3(all P<0.05).After intervention,the expression of PI3K and p-Akt was upregulated,while Caspase-3 was downregulated in the LSI+AOH group and the HSI+AOH group(all P<0.01). ·CONCLUSION:SI ameliorates glucocorticoid-induced RGCs injury,potentially by activating phosphorylated Akt(p-Akt)and subsequently inhibiting Caspase-3-mediated apoptosis.These neuroprotective effects appear to be dose-dependent.