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水溶性二氢嘧啶硫酮衍生物对紫外线B诱导的人角膜上皮细胞光损伤的细胞保护作用

Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage.

作者信息

Du Enming, Pu Guojuan, He Siyu, Qin Fangyuan, Wang Yange, Wang Gang, Song Zongming, Zhang Junjie, Tao Ye

机构信息

Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Henan University School of Medicine, Henan Provincial People's Hospital, Zhengzhou, China.

Lab of Visual Cell Differentiation and Modulation, Basic Medical College, Zhengzhou University, Zhengzhou, China.

出版信息

Front Pharmacol. 2021 Oct 20;12:732833. doi: 10.3389/fphar.2021.732833. eCollection 2021.

DOI:10.3389/fphar.2021.732833
PMID:34744716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8570246/
Abstract

Excessive UV-B exposure is well known to be a risk factor for corneal phototoxicity including direct DNA damage and disturbances in the antioxidant balance. Here, we showed a successful synthesis of a water-soluble and biocompatible small molecule with dihydropyrimidinthione skeleton, which could effectively protect human corneal epithelial (HCE-2) cells from UV-B damage. In separate experiments, absorbed UV-B rays and exhibited scavenging activity against intracellular ROS induced by UV-B radiation, thereby reducing the levels of DNA fragmentation. Additionally, UV-B exposure increased the expression of cleaved caspase-3, as well as the ratio of Bax/Bcl-2 at protein levels, while pretreatment with significantly reversed these changes. To the best of our knowledge, this is the first report of a study based on dihydropyrimidinthione derivatives to develop a promising eye drops, which may well find extensive applications in UV-B caused corneal damage.

摘要

众所周知，过度暴露于UV-B是角膜光毒性的一个风险因素，包括直接的DNA损伤和抗氧化平衡的紊乱。在此，我们展示了一种成功合成的具有二氢嘧啶硫酮骨架的水溶性且生物相容的小分子，它可以有效地保护人角膜上皮（HCE-2）细胞免受UV-B损伤。在单独的实验中，其吸收UV-B射线并表现出对UV-B辐射诱导的细胞内活性氧的清除活性，从而降低DNA片段化水平。此外，UV-B暴露增加了裂解的caspase-3的表达以及蛋白质水平上Bax/Bcl-2的比率，而用该小分子预处理可显著逆转这些变化。据我们所知，这是第一项基于二氢嘧啶硫酮衍生物开发有前景的眼药水的研究报告，其很可能在UV-B引起的角膜损伤中得到广泛应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab79/8570246/e4145dda9c18/fphar-12-732833-g006.jpg
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本文引用的文献

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Protective Effect of Vitamin C against Infancy Rat Corneal Injury Caused by Acute UVB Irradiation.维生素 C 对急性 UVB 照射致幼鼠角膜损伤的保护作用。
Biomed Res Int. 2020 May 25;2020:8089273. doi: 10.1155/2020/8089273. eCollection 2020.
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UV-B-Induced Inflammasome Activation Can Be Prevented by Cis-Urocanic Acid in Human Corneal Epithelial Cells.
UV-B 诱导的炎症小体激活可被顺式尿刊酸在人角膜上皮细胞中所预防。
Invest Ophthalmol Vis Sci. 2020 Apr 9;61(4):7. doi: 10.1167/iovs.61.4.7.
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NAD precursors protect corneal endothelial cells from UVB-induced apoptosis.NAD 前体可保护角膜内皮细胞免受 UVB 诱导的凋亡。
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Protective effect of PACAP against ultraviolet B radiation-induced human corneal endothelial cell injury.PACAP 对紫外线 B 辐射诱导的人眼角膜内皮细胞损伤的保护作用。
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Methods of Assessment of the Corneas of the Eyes Laboratory Rabbits Exposed to Solar Ultraviolet-B Radiation.暴露于太阳紫外线-B 辐射下的实验兔眼睛角膜评估方法。
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High Throughput Preparation of UV-Protective Polymers from Essential Oil Extracts via the Biginelli Reaction.通过比格利尼反应从精油提取物中高通量制备具有紫外线防护性能的聚合物。
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