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局部 8-氧代-2'-脱氧鸟苷与皮质类固醇在眼碱性烧伤模型中的疗效比较。

Comparison of therapeutic effects between topical 8-oxo-2'-deoxyguanosine and corticosteroid in ocular alkali burn model.

机构信息

Department of Ophthalmology, Gil Medical Center, Gachon University College of Medicine, 1198, Guwol-dong, Namdong-Gu, Incheon, 21565, Korea.

Fight Against Angiogenesis Related Blindness (FARB) Laboratory, Seoul National University Hospital, Seoul, Korea.

出版信息

Sci Rep. 2021 Mar 25;11(1):6909. doi: 10.1038/s41598-021-86440-7.

Abstract

We compared the therapeutic effects of topical 8-oxo-2'-deoxyguanosine (8-oxo-dG) and corticosteroid in a murine ocular alkali burn model. (n = 128) The corneal alkali burn model was established by applying 0.1 N sodium hydroxide (NaOH), followed by treatment with 8-oxo-dG, 0.1% fluorometholone (FML), 1% prednisolone acetate (PDE), or phosphate-buffered saline (PBS) twice daily. One week later, the clinical and histological status of the cornea were assessed. Transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase as well as the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the cornea, were assayed. The 8-oxo-dG and PDE groups showed marked improvements in corneal integrity and clarity when compared with the PBS group (each p < 0.01). The numbers of cells stained for neutrophil elastase and F4/80-positive inflammatory cells were significantly decreased, with levels of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, and total ROS/RNS amounts markedly reduced in the 8-oxo-dG, FML, and PDE groups (each p < 0.05). Levels of NADPH oxidase type 2 and 4 were substantially more repressed in the 8-oxo-dG-treated group than in the PDE-treated group (each p < 0.05). Topical 8-oxo-dG showed excellent therapeutic effects that were comparable with those treated with topical PDE in a murine ocular alkali burn model.

摘要

我们比较了局部 8-氧-2'-脱氧鸟苷(8-氧-dG)和皮质类固醇在小鼠眼碱烧伤模型中的治疗效果。(n=128)通过应用 0.1 N 氢氧化钠(NaOH)建立角膜碱烧伤模型,随后用 8-氧-dG、0.1%氟米龙(FML)、1%醋酸泼尼松龙(PDE)或磷酸盐缓冲盐水(PBS)每日两次治疗。一周后,评估角膜的临床和组织学状况。检测角膜中炎症细胞因子和烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的转录水平以及活性氧(ROS)和活性氮(RNS)的水平。与 PBS 组相比,8-氧-dG 和 PDE 组的角膜完整性和清晰度明显改善(p<0.01)。中性粒细胞弹性蛋白酶染色的细胞数量和 F4/80 阳性炎症细胞数量明显减少,8-氧-dG、FML 和 PDE 组白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α和总 ROS/RNS 水平显著降低(p<0.05)。8-氧-dG 处理组 NADPH 氧化酶 2 和 4 的水平明显低于 PDE 处理组(p<0.05)。在小鼠眼碱烧伤模型中,局部 8-氧-dG 显示出与局部 PDE 相当的优异治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fbc/7994716/541751d74a1e/41598_2021_86440_Fig1_HTML.jpg

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