Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been testified to be involved in the development of retinopathy of prematurity (ROP), which can cause childhood visual impairment. Whether brusatol, an Nrf2 inhibitor, could be utilized to treat ROP was unknown. The oxygen-induced retinopathy rat model was established to mimic ROP, which was further intravitreal administrated with brusatol. Vessel morphology and microglial activation in the retina were assessed with histology analysis. The relative expression levels of angiogenesis and inflammation-related molecules were detected with Western blot and real-time polymerase chain reaction methods. Intravitreal brusatol administration could alleviate both angiogenesis and microgliosis induced by hyperoxia, along with down-regulation of vascular endothelial growth factor, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, cluster of differentiation molecule 11B, tumor necrosis factor alpha, inducible nitric oxide synthase, glial fibrillary acidic protein, and IBA-1 expression. It was further revealed that Nrf2 and heme oxygenease-1 were diminished by brusatol administration. The results demonstrate the potential of intravitreal brusatol deliver to treat ROP with down-regulation of angiogenesis and microgliosis.

中文翻译：

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Nrf2 抑制剂 brusatol 在氧诱导的早产儿视网膜病变大鼠模型中具有保护作用

核因子-红细胞 2 相关因子 2 (Nrf2) 已被证明与早产儿视网膜病变 (ROP) 的发展有关，这可导致儿童视力障碍。一种 Nrf2 抑制剂 brusatol 是否可用于治疗 ROP 尚不清楚。建立氧诱导的视网膜病变大鼠模型以模拟 ROP，进一步玻璃体内给予 brusatol。用组织学分析评估视网膜中的血管形态和小胶质细胞活化。采用蛋白质印迹法和实时聚合酶链反应法检测血管生成和炎症相关分子的相对表达水平。玻璃体内注射芸香醇可以减轻高氧诱导的血管生成和小胶质细胞增生，同时下调血管内皮生长因子，血管内皮生长因子受体 (VEGFR)-1、VEGFR-2、分化分子簇 11B、肿瘤坏死因子 α、诱导型一氧化氮合酶、胶质纤维酸性蛋白和 IBA-1 表达。进一步揭示了 Nrf2 和血红素氧化酶-1 被 brusatol 给药减少。结果证明了玻璃体内布鲁索托递送治疗ROP的潜力，其具有下调血管生成和小胶质细胞增生的作用。