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漆黄素通过抑制青光眼DBA/2J小鼠模型中的炎症反应来挽救视网膜功能。

Fisetin rescues retinal functions by suppressing inflammatory response in a DBA/2J mouse model of glaucoma.

作者信息

Li Linlin, Qin Jie, Fu Tingting, Shen Jiaxiang

机构信息

Department of Ophthalmology, People's Hospital of Rizhao, No. 126 Tai'an Road, Donggang District, Rizhao, 276800, Shandong, China.

Department of Ophthalmology, Rizhao Central Hospital of Shandong, No. 66 Wanghai Road, Donggang District, Rizhao, 276800, Shandong, China.

出版信息

Doc Ophthalmol. 2019 Apr;138(2):125-135. doi: 10.1007/s10633-019-09676-9. Epub 2019 Feb 11.

Abstract

PURPOSE

Glaucoma is a common chronic neurodegenerative disease, which could lead to visual loss. In this study, we aimed to investigate whether fisetin, a natural flavone with anti-inflammatory and antioxidant properties, is able to alleviate glaucoma.

METHODS

We employed a DBA/2J mouse model which was treated with or without fisetin. Pattern electroretinogram (P-ERG), visual evoked potentials (VEPs) and intraocular pressure (IOP) were evaluated. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) were used to measure the expression levels of TNF-α, IL-1β and IL-6. Western blotting was performed to assess the activation of nuclear factor kappa-B (NF-κB).

RESULTS

We found that DBA/2J mice treated with fisetin (10-30 mg/kg) showed improved P-ERG and VEP amplitudes and reduced IOP compared to untreated DBA/2J mice. In addition, there were more survived retinal ganglion cells (RGCs) and less activated microglia in fisetin-treated DBA/2J mice than those in untreated mice. Furthermore, secreted protein levels and mRNA levels of TNF-α, IL-1β and IL-6 were significantly repressed by fisetin. The phosphorylated p65 level in the nucleus was dramatically reduced in fisetin-treated mice compared to it in untreated mice. Our results demonstrate that fisetin may exert its function through regulating cytokine productions and inhibiting NF-κB activation in the retina.

CONCLUSION

In conclusion, fisetin is able to promote the visual functions of DBA/2J mice by inhibiting NF-κB activation.

摘要

目的

青光眼是一种常见的慢性神经退行性疾病,可导致视力丧失。在本研究中,我们旨在调查漆黄素(一种具有抗炎和抗氧化特性的天然黄酮类化合物)是否能够缓解青光眼。

方法

我们使用了DBA/2J小鼠模型,对其进行了有无漆黄素的处理。评估了图形视网膜电图(P-ERG)、视觉诱发电位(VEP)和眼压(IOP)。采用定量实时聚合酶链反应和酶联免疫吸附测定(ELISA)来测量肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的表达水平。进行蛋白质免疫印迹法以评估核因子κB(NF-κB)的激活情况。

结果

我们发现,与未处理的DBA/2J小鼠相比,用漆黄素(10 - 30毫克/千克)处理的DBA/2J小鼠的P-ERG和VEP振幅有所改善,眼压降低。此外,与未处理的小鼠相比,用漆黄素处理的DBA/2J小鼠中存活的视网膜神经节细胞(RGC)更多,小胶质细胞的激活更少。此外,漆黄素显著抑制了TNF-α、IL-1β和IL-6的分泌蛋白水平和mRNA水平。与未处理的小鼠相比,用漆黄素处理的小鼠细胞核中磷酸化的p65水平显著降低。我们的结果表明,漆黄素可能通过调节细胞因子的产生和抑制视网膜中NF-κB的激活来发挥其功能。

结论

总之,漆黄素能够通过抑制NF-κB的激活来促进DBA/2J小鼠的视觉功能。

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