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利拉鲁肽上调硫氧还蛋白减轻高糖诱导的 Muller 细胞凋亡及其机制研究。

Liraglutide Up-regulation Thioredoxin Attenuated Müller Cells Apoptosis in High Glucose by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.

机构信息

Department of Histology and Embryology, College of Basic Medicine, Dalian Medical University , Dalian, China.

Department of Anatomy, Jiangsu College of Nursing , Huai'an, Jiangsu Province, China.

出版信息

Curr Eye Res. 2020 Oct;45(10):1283-1291. doi: 10.1080/02713683.2020.1737137. Epub 2020 Mar 17.

Abstract

: Diabetic retinopathy (DR) has become one of the most important complications of diabetes which is the leading cause of vision impairment and blindness all over the world. Increasing evidence shows that reactive gliosis are basic pathological features of early DR. The study was aimed to explore the protective effect and mechanism of Liraglutide (LIRA) which has similar properties to Glucagon-like peptide-1 (GLP-1) on Müller cell damage induced by diabetes. : , the Müller cell was cultured in high glucose (HG) to establish the model of diabetic retinopathy. The apoptosis was detected using flow cytometry. Western blot and immunofluorescence were used to detect the expression of related proteins. DCFH-DA probe was used to detect the ROS generation. : The data showed that the apoptosis and the expression of GFAP were increased significantly with HG treatment. However, the apoptosis percentage and the expression of GFAP were decreased after LIRA treatment. Moreover, the expression of p-Erk/Nrf2/Trx-signaling pathway proteins was also up-regulated and the generation of ROS was decreased after LIRA treatment which was inhibited after treatment with U0126 (Erk inhibitor). Besides, endoplasmic reticulum stress (ER stress) related proteins were up-regulated after Trx down-regulation by transfection with sh-RNA. : LIRA could protect Müller cells from HG-induced damage via activating p-Erk pathway through increasing Trx expression which attenuated oxidative stress and ER stress. Trx could play a key role in the process.

摘要

糖尿病性视网膜病变(DR)已成为糖尿病的最重要并发症之一,是全世界视力损害和失明的主要原因。越来越多的证据表明,反应性神经胶质增生是早期 DR 的基本病理特征。本研究旨在探讨类似胰高血糖素样肽-1(GLP-1)的利拉鲁肽(LIRA)对糖尿病诱导的 Müller 细胞损伤的保护作用及其机制。

方法

将 Müller 细胞在高糖(HG)中培养,建立糖尿病性视网膜病变模型。采用流式细胞术检测细胞凋亡。采用 Western blot 和免疫荧光法检测相关蛋白的表达。采用 DCFH-DA 探针检测 ROS 的产生。

结果

数据显示,HG 处理后细胞凋亡和 GFAP 表达显著增加,而 LIRA 处理后细胞凋亡百分比和 GFAP 表达降低。此外,LIRA 处理后 p-Erk/Nrf2/Trx 信号通路蛋白表达上调,ROS 生成减少,用 U0126(Erk 抑制剂)处理后则被抑制。另外,用 sh-RNA 转染下调 Trx 后内质网应激(ER 应激)相关蛋白表达上调。

结论

LIRA 可通过增加 Trx 表达激活 p-Erk 通路,从而保护 Müller 细胞免受 HG 诱导的损伤,减轻氧化应激和 ER 应激。Trx 可能在该过程中发挥关键作用。

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