Protective effects of empagliflozin against NMDA-induced excitotoxicity in the rat retina.

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2025-07-08 DOI:10.1016/j.neulet.2025.138315

Momoka Ota, Akane Morita, Toshihide Kashihara, Tsutomu Nakahara

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引用次数: 0

Abstract

Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor used in patients with type 2 diabetes, exerts various beneficial effects, including anti-inflammatory and antioxidant properties, in addition to its glucose-lowering effect. In this study, we examined whether EMPA protects against N-methyl-d-aspartic acid (NMDA)-induced retinal excitotoxicity and the mechanisms underlying its protective effects. Male Sprague-Dawley rats (7-8 weeks old) were used in this study. The number of cells in the ganglion cell layer (GCL) decreased 7 days after intravitreal injection of NMDA (50 nmol). Simultaneous intravitreal injection of EMPA (50 and 100 nmol) and NMDA reduced NMDA-induced cell loss in a dose-dependent manner. The protective effect of EMPA was significantly attenuated by the AMP-activated protein kinase (AMPK) inhibitor, compound C (10 nmol). NMDA increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in the GCL 6 h after injection, and the response was significantly, but not completely, attenuated by EMPA. These results suggest that EMPA protects against NMDA-induced retinal excitotoxicity in rats. The protective effect of EMPA may be partly attributed to the activation of the AMPK pathway and inhibition of neuronal cell apoptosis.

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恩格列净对nmda诱导大鼠视网膜兴奋性毒性的保护作用。

恩帕列净（EMPA）是一种用于2型糖尿病患者的钠-葡萄糖共转运蛋白2抑制剂，除了具有降血糖作用外，还具有多种有益作用，包括抗炎和抗氧化特性。在这项研究中，我们研究了EMPA是否对n -甲基-d-天冬氨酸（NMDA）诱导的视网膜兴奋性毒性及其保护作用的机制。本研究采用雄性Sprague-Dawley大鼠（7-8 周龄）。玻璃体内注射NMDA(50 nmol) 7 d后，神经节细胞层（GCL）细胞数量减少。同时玻璃体内注射EMPA（50和100 nmol）和NMDA以剂量依赖的方式减少NMDA诱导的细胞损失。EMPA活化蛋白激酶（AMPK）抑制剂化合物C（10 nmol）显著减弱EMPA的保护作用。NMDA增加了注射后 h GCL 6中末端脱氧核苷酸转移酶介导的dUTP镍端标记（TUNEL）阳性细胞的数量，而EMPA明显但不完全减弱了这种反应。提示EMPA对nmda诱导的大鼠视网膜兴奋性毒性具有保护作用。EMPA的保护作用可能部分归因于激活AMPK通路和抑制神经元细胞凋亡。

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来源期刊

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

期刊介绍： Neuroscience Letters is devoted to the rapid publication of short, high-quality papers of interest to the broad community of neuroscientists. Only papers which will make a significant addition to the literature in the field will be published. Papers in all areas of neuroscience - molecular, cellular, developmental, systems, behavioral and cognitive, as well as computational - will be considered for publication. Submission of laboratory investigations that shed light on disease mechanisms is encouraged. Special Issues, edited by Guest Editors to cover new and rapidly-moving areas, will include invited mini-reviews. Occasional mini-reviews in especially timely areas will be considered for publication, without invitation, outside of Special Issues; these un-solicited mini-reviews can be submitted without invitation but must be of very high quality. Clinical studies will also be published if they provide new information about organization or actions of the nervous system, or provide new insights into the neurobiology of disease. NSL does not publish case reports.