摘要
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(10μmol/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。
AIM:To investigate the protective effect ofβ-sitosterol on retinal structure and function and its underlying molecular mechanism in a sodium iodate(NaIO 3)-induced mouse model of dry age-related macular degeneration(ARMD).METHODS:A dry ARMD mouse model was established by NaIO 3 injection.The therapeutic effect ofβ-sitosterol intervention was evaluated using fundus photography,histopathology(HE staining),and electroretinography(ERG).Network pharmacology was employed to screen potential targets ofβ-sitosterol in ARMD,and molecular docking was used to validate the binding ability betweenβ-sitosterol and these targets.The impact ofβ-sitosterol on ARPE-19 cell viability and apoptosis pathways was analyzed using CCK-8 assay,Hoechst staining,and Western blotting.RESULTS:Theβ-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 ofβ-sitosterol;molecular docking demonstrated thatβ-sitosterol binds to PON1 via hydrophobic interactions and hydrogen bonds.In vitro experiments showed thatβ-sitosterol(10μmol/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:Theβ-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 ofβ-sitosterol as a novel therapeutic agent for dry ARMD.
作者
栗小丽
王伟
李娟
赵朝霞
Li Xiaoli;Wang Wei;Li Juan;Zhao Zhaoxia(Aier Eye Hospital Affiliated to Henan University,Zhengzhou Aier Eye Hospital,Zhengzhou 450000,Henan Province,China)
出处
《国际眼科杂志》
2025年第11期1728-1734,共7页
International Eye Science
