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硫化氢通过抑制 ROS 介导的内质网应激-CHOP 凋亡信号保护视网膜免受蓝光诱导的光损伤和变性。

Hydrogen sulfide protects retina from blue light-induced photodamage and degeneration via inhibiting ROS-mediated ER stress-CHOP apoptosis signal.

机构信息

School of Life Sciences, Lanzhou University, Lanzhou, People's Republic of China.

Lanzhou University Second Hospital, Lanzhou, People's Republic of China.

出版信息

Redox Rep. 2022 Dec;27(1):100-110. doi: 10.1080/13510002.2022.2069534.

Abstract

Hydrogen sulfide (HS) is a small reducing gas molecule with various biological functions such as anti-oxidative, anti-apoptotic and anti-inflammatory activities. In this study, we investigated the therapeutic effects of exogenous HS in the experimental models of retinal photodamage in vivo and in vitro. Rats with open eyelids were pretreated with HS (80120 μmol/kg) for 10 days and then continuously exposed to blue light (435445nm, 11.2W/m2) for 8 h to establish in vivo experimental model. ARPE-19 cells were pretreated with HS and then exposed to blue light to establish in vitro experimental model. In vivo experiments, HS significantly ameliorated blue light-induced retinal oxidative stress, apoptosis and degeneration. Moreover, HS inhibited the activation of blue light-induced endoplasmic reticulum (ER) stress CHOP apoptotic signaling. In vitro experiments, HS improved blue light-induced oxidative stress and oxidative damage. HS inhibited ROS-mediated activation of ER stress CHOP apoptotic signaling. HS alleviated blue light-induced apoptosis and increases cell viability. The ER stress inhibitor 4-PBA alleviated blue light-induced apoptosis and increases cell viability. Taken together, these results indicate that HS can inhibit ROS-mediated ER stress-CHOP apoptosis signal, thereby alleviating blue light-triggered retinal apoptosis and degeneration.

摘要

硫化氢(HS)是一种具有多种生物学功能的小分子还原性气体,如抗氧化、抗细胞凋亡和抗炎活性。在这项研究中,我们研究了外源性 HS 在体内和体外视网膜光损伤实验模型中的治疗作用。大鼠暴露于开眼状态下,经 HS(80120 μmol/kg)预处理 10 天,然后持续暴露于蓝光(435445nm,11.2W/m2)8 小时,建立体内实验模型。ARPE-19 细胞经 HS 预处理后再暴露于蓝光,建立体外实验模型。在体内实验中,HS 显著改善了蓝光诱导的视网膜氧化应激、细胞凋亡和变性。此外,HS 抑制了蓝光诱导的内质网(ER)应激 CHOP 凋亡信号的激活。在体外实验中,HS 改善了蓝光诱导的氧化应激和氧化损伤。HS 抑制了 ROS 介导的 ER 应激 CHOP 凋亡信号的激活。HS 减轻了蓝光诱导的细胞凋亡并增加了细胞活力。ER 应激抑制剂 4-PBA 减轻了蓝光诱导的细胞凋亡并增加了细胞活力。综上所述,这些结果表明 HS 可以抑制 ROS 介导的 ER 应激-CHOP 凋亡信号,从而减轻蓝光触发的视网膜细胞凋亡和变性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcdd/9067965/73745c5b4705/YRER_A_2069534_F0001_OC.jpg

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