Li Lin, Wang YeFei, Qin XiuHong, Zhang Jing, Zhang ZhenZhen
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Ophthalmology, First Affiliated Hospital of Dalian Medical University, DaLian, Liaoning Province, China.
Mol Vis. 2018 Nov 25;24:746-758. eCollection 2018.
To investigate whether echinacoside (ECH) protects the retina against ischemia/reperfusion (I/R) injury and the underlying mechanisms.
Adult male Wistar rats were randomly divided into four groups: sham, sham plus ECH, I/R plus vehicle, and I/R plus ECH. Before the retinal I/R injury produced by high intraocular pressure (HOP), ECH was administered (20 mg/kg daily) for 7 days. The level of retinal cell damage was evaluated using Fluoro-Gold (FG) retrograde labeling and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) analysis 7 days after I/R. Optic nerve histology was analyzed with transmission electron microscopy. Levels of retinal malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. The expression of apoptosis-associated factors (Apaf-1, Parp, and Bad) were analyzed with western blotting and quantitative real-time PCR (qPCR). The production of proinflammatory cytokines (tumor necrosis factor-α [TNFα], interleukin-1 beta [IL-1β], and IL-6) was analyzed with enzyme-linked immunosorbent assay (ELISA) 7 days after the I/R injury as well.
The administration of ECH not only preserved retinal morphology but also attenuated retinal inflammation and apoptosis at 7 days after the I/R injury and decreased I/R-induced oxidative stress in the retina statistically significantly.
ECH protected against I/R-induced retinal injury, via activation of antioxidant enzymes and suppression of inflammation. Therefore, ECH could be a potential therapeutic candidate for the treatment and management of I/R retinal diseases.
研究紫锥菊苷(ECH)是否能保护视网膜免受缺血/再灌注(I/R)损伤及其潜在机制。
成年雄性Wistar大鼠随机分为四组:假手术组、假手术+ECH组、I/R+溶剂组和I/R+ECH组。在通过高眼压(HOP)产生视网膜I/R损伤前,给予ECH(每日20mg/kg),持续7天。I/R损伤7天后,使用荧光金(FG)逆行标记和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)分析评估视网膜细胞损伤水平。用透射电子显微镜分析视神经组织学。测定视网膜丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)的水平。用蛋白质免疫印迹法和定量实时PCR(qPCR)分析凋亡相关因子(Apaf-1、Parp和Bad)的表达。I/R损伤7天后,还用酶联免疫吸附测定(ELISA)分析促炎细胞因子(肿瘤坏死因子-α [TNFα]、白细胞介素-1β [IL-1β]和IL-6)的产生。
给予ECH不仅保留了视网膜形态,还减轻了I/R损伤7天后的视网膜炎症和凋亡,并在统计学上显著降低了I/R诱导的视网膜氧化应激。
ECH通过激活抗氧化酶和抑制炎症来保护视网膜免受I/R诱导的损伤。因此,ECH可能是治疗和管理I/R视网膜疾病的潜在治疗候选药物。