目的：探讨大豆异黄酮(SI)对糖皮质激素诱导的高眼压(AOH)大鼠视网膜神经节细胞(RGCs)的保护作用及其对PI3K/Akt/Caspase-3凋亡通路的调控机制。

方法：SD大鼠48只(48眼)随机均分为正常对照组、高眼压对照组(AOH对照组)、低剂量SI干预组[LSI+AOH组，360 mg/(kg·d)]和高剂量SI干预组[HSI+AOH组，540 mg/(kg·d)]。除正常对照组外，其余组通过结膜下注射地塞米松建立AOH模型。造模第3 wk起，LSI+AOH组和HSI+AOH组腹腔注射相应剂量SI持续至4 wk。检测眼压、RGCs数量、PI3K/p-Akt/Caspase-3蛋白表达及炎症因子水平。

结果：AOH对照组眼压显著高于正常对照组(P<0.01)； SI干预后，LSI+AOH组和HSI+AOH组眼压较AOH对照组显著降低(均P<0.01)。AOH对照组RGCs数量较对照组显著减少(P<0.01)，而LSI+AOH组和HSI+AOH组较AOH对照组显著增加(均P<0.01)。与正常对照组相比，AOH对照组PI3K、p-Akt表达降低而Caspase-3升高(均P<0.05)； 干预后，LSI+AOH组和HSI+AOH组PI3K、p-Akt表达升高且Caspase-3降低(均P<0.01)。

结论：SI干预显著上调PI3K表达并促进Akt磷酸化(p-Akt)，同时抑制Caspase-3活化，减轻AOH诱导的RGCs损伤，其神经保护效应具有剂量依赖性。

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.