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Research Article

Celastrol通过激活Nrf2信号通路保护RPE细胞免受氧化应激诱导的细胞死亡

卷 19, 期 3, 2019

页: [172 - 182] 页: 11

弟呕挨: 10.2174/1566524019666190424131704

价格: $65

摘要

目的：对视网膜色素上皮（RPE）细胞和炎症的氧化应激与年龄相关性黄斑变性（AMD）的发病机制密切相关。 Celastrol是一种从雷公藤（Tripterygium wilfordii）根中分离出来的天然化合物。已经证明，Celastrol在多种疾病模型中具有有效的抗炎和抗肿瘤作用。本研究的目的是测试celastrol在RPE细胞中的抗氧化作用并研究其潜在机制。 方法：用过氧化氢（H2O2）和甲萘醌单独或与celastrol联合处理ARPE-19细胞。分别通过CCK-8和TUNEL测定检查细胞活力和细胞凋亡。通过蛋白质印迹法测定Nrf2及其靶基因如GCLM和HO-1的表达。通过用编码针对Nrf2的shRNA的慢病毒转染ARPE-19细胞来完成Nrf2的敲低。通过实时定量PCR和Western印迹确定敲低效率。 结果：用celastrol处理ARPE-19细胞显着减弱了H2O2和甲萘醌的毒性作用。用celastrol治疗增强了转录因子Nrf2及其靶标，GCLM和HO-1的表达。通过shRNA敲低Nrf2表达部分地消除了celastrol的保护作用。 L-丁硫氨酸-S，R-亚砜亚胺（BSO）对谷胱甘肽合成的化学抑制完全消除了celastrol对H2O2和甲萘醌诱导的损伤的保护作用。然而，ZnPPIX对HO-1活性的化学抑制并未降低celastrol的保护作用。 结论：本研究提供的证据表明，用celastrol处理RPE细胞通过激活Nrf2信号通路和上调GCLM表达显示出对氧化损伤的有效保护作用。该发现表明，celastrol可用作氧化应激相关眼病的潜在治疗剂，例如AMD。

关键词: Celastrol，视网膜色素上皮细胞，氧化应激，Nrf2信号传导，年龄相关性黄斑变性，RPE细胞。

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