Celastrol protects mouse retinas from bright light-induced degeneration through inhibition of oxidative stress and inflammation
Celastrol protects mouse retinas from bright light-induced degeneration through inhibition of oxidative stress and inflammation
复制标题
雷公藤红醇通过抑制氧化应激和炎症来保护小鼠视网膜免受强光引起的退化
DOI：
10.1186/s12974-016-0516-8
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发表时间：
2016-02-27
影响因子：
9.3
通讯作者：
Chen, Yu
中科院分区：
文献类型：
--
作者：
Bian, Minjuan;Du, Xiaoye;Chen, Yu
研究背景光感受器死亡可导致多种视网膜变性疾病的视力损害。保护光感受器免于退化的疗法仍有待开发。雷公藤红素的抗炎、抗氧化应激和神经保护作用已在多种疾病模型中得到证实。本研究旨在探讨雷公藤红素的光感受器保护作用。MethodsBright light诱导的BALB/c小鼠视网膜变性，和视网膜的形态，功能和分子的变化进行了评估，在没有和存在的雷公藤红素treatment.ResultsSignificant的形态和功能的保护观察到的结果雷公藤红素治疗在明亮的光暴露的BALB/c小鼠。雷公藤红素治疗导致感光细胞中细胞死亡的抑制，视网膜色素上皮和光感受器中氧化应激的缓解，促炎基因的视网膜表达的下调，以及视网膜中小胶质细胞活化和胶质细胞增生的抑制。此外，发现在光暴露的BALB/c小鼠的视网膜脉管系统中诱导白细胞停滞，其通过雷公藤红素处理显著减弱。在体外，雷公藤红素衰减全反式视黄醇诱导的氧化应激培养的APRE 19细胞。此外，雷公藤红素治疗显着抑制脂多糖刺激的促炎基因在APRE 19和RAW264.7 cells.ConclusionsThe结果首次证明，雷公藤红素通过抑制视网膜氧化应激和炎症，防止光诱导的视网膜变性。
BackgroundPhotoreceptor death leads to vision impairment in several retinal degenerative disorders. Therapies protecting photoreceptor from degeneration remain to be developed. Anti-inflammation, anti-oxidative stress, and neuroprotective effects of celastrol have been demonstrated in a variety of disease models. The current study aimed to investigate the photoreceptor protective effect of celastrol.MethodsBright light-induced retinal degeneration in BALB/c mice was used, and morphological, functional, and molecular changes of retina were evaluated in the absence and presence of celastrol treatment.ResultsSignificant morphological and functional protection was observed as a result of celastrol treatment in bright light-exposed BALB/c mice. Celastrol treatment resulted in suppression of cell death in photoreceptor cells, alleviation of oxidative stress in the retinal pigment epithelium and photoreceptors, downregulation of retinal expression of proinflammatory genes, and suppression of microglia activation and gliosis in the retina. Additionally, leukostasis was found to be induced in the retinal vasculature in light-exposed BALB/c mice, which was significantly attenuated by celastrol treatment. In vitro, celastrol attenuated all-trans-retinal-induced oxidative stress in cultured APRE19 cells. Moreover, celastrol treatment significantly suppressed lipopolysaccharides-stimulated expression of proinflammatory genes in both APRE19 and RAW264.7 cells.ConclusionsThe results demonstrated for the first time that celastrol prevents against light-induced retinal degeneration through inhibition of retinal oxidative stress and inflammation.