目的：探讨β-谷甾醇对碘酸钠(NaIO₃)诱导的干性年龄相关性黄斑变性(ARMD)模型小鼠视网膜结构和功能的保护作用及其分子机制。

方法：建立NaIO₃诱导的小鼠干性ARMD模型，通过眼底照相、组织病理学(HE染色)及视网膜电图(ERG)评估β-谷甾醇干预效果。利用网络药理学筛选β-谷甾醇在ARMD中的潜在作用靶点，并通过分子对接技术验证β-谷甾醇与潜在靶点的结合能力。通过CCK-8、Hoechst染色及Western blot分析β-谷甾醇对ARPE-19细胞活性、凋亡通路的影响。

结果：β-谷甾醇显著减轻模型小鼠视网膜结构损伤(使视网膜及外核层厚度增加，黄白色渗出灶减少)及功能损伤(a波、b波振幅部分恢复)。网络药理学筛选出β-谷甾醇的关键作用靶点PON1； 分子对接显示β-谷甾醇通过疏水键及氢键结合PON1。细胞实验表明β-谷甾醇(10 μmol/L)可提升ARPE-19细胞活性(P<0.01)，减少凋亡(P<0.01)，并上调PON1表达(P<0.01)，同时抑制cleaved-Caspase3表达(P<0.01)。

结论：β-谷甾醇可能通过调控PON1 抑制Caspase3依赖性凋亡通路，从而减轻氧化应激诱导的视网膜损伤，为干性ARMD治疗开发新药物提供实验依据。

METHODS: A dry ARMD mouse model was established by NaIO₃ injection. The therapeutic effect of β-sitosterol intervention was evaluated using fundus photography, histopathology(HE staining), and electroretinography(ERG). Network pharmacology was employed to screen potential targets of β-sitosterol in ARMD, and molecular docking was used to validate the binding ability between β-sitosterol and these targets. The impact of β-sitosterol on ARPE-19 cell viability and apoptosis pathways was analyzed using CCK-8 assay, Hoechst staining, and Western blotting.

RESULTS: The β-sitosterol significantly alleviated structural damage in the retinas of model mice(increased retinal and outer nuclear layer thickness, reduced yellowish-white drusen-like deposits)and functional impairment(partial restoration of a-wave and b-wave amplitudes). Network pharmacology identified PON1 as a key target of β-sitosterol; molecular docking demonstrated that β-sitosterol binds to PON1 via hydrophobic interactions and hydrogen bonds. In vitro experiments showed that β-sitosterol(10 μmol/L)significantly increased ARPE-19 cell viability(P<0.01), reduced apoptosis(P<0.01), upregulated PON1 expression(P<0.01), and concurrently suppressed cleaved-Caspase3 expression(P<0.01).

CONCLUSION: The β-sitosterol likely protects against oxidative stress-induced retinal damage by modulating PON1 to suppress the Caspase3-dependent apoptotic pathway. These findings provide experimental evidence supporting the development of β-sitosterol as a novel therapeutic agent for dry ARMD.