Han Ning, Yu Li, Song Zhidu, Luo Lifu, Wu Yazhen
Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Department of Ocular Fundus Disease, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Mol Med Rep. 2015 Jul;12(1):1098-106. doi: 10.3892/mmr.2015.3540. Epub 2015 Mar 24.
Neural injury is associated with the development of diabetic retinopathy. Müller cells provide structural and metabolic support for retinal neurons. High glucose concentrations are known to induce Müller cell activity. Agmatine is an endogenous polyamine, which is enzymatically formed in the mammalian brain and has exhibited neuroprotective effects in a number of experimental models. The aims of the present study were to investigate whether agmatine protects Müller cells from glucose-induced damage and to explore the mechanisms underlying this process. Lactate dehydrogenase activity and tumor necrosis factor-α mRNA expression were significantly reduced in Müller cells exposed to a high glucose concentration, following agmatine treatment, compared with cells not treated with agmatine. In addition, agmatine treatment inhibited glucose-induced Müller cell apoptosis, which was associated with the regulation of Bax and Bcl-2 expression. Agmatine treatment suppressed glucose-induced phosphorylation of mitogen-activated protein kinase (MAPK) protein in Müller cells. The present study demonstrated that the protective effects of agmatine on Müller cells were inhibited by N-methyl-D-aspartic acid (NMDA). The results of the present study suggested that agmatine treatment protects Müller cells from high-concentration glucose-induced cell damage. The underlying mechanisms may relate to the anti-inflammatory and antiapoptotic effects of agmatine, as well as to the inhibition of the MAPK pathway, via NMDA receptor suppression. Agmatine may be of use in the development of novel therapeutic approaches for patients with diabetic retinopathy.
神经损伤与糖尿病视网膜病变的发展相关。穆勒细胞为视网膜神经元提供结构和代谢支持。已知高葡萄糖浓度会诱导穆勒细胞活性。胍丁胺是一种内源性多胺，在哺乳动物大脑中通过酶促形成，并且在许多实验模型中已表现出神经保护作用。本研究的目的是调查胍丁胺是否能保护穆勒细胞免受葡萄糖诱导的损伤，并探索这一过程的潜在机制。与未用胍丁胺处理的细胞相比，用胍丁胺处理后，暴露于高葡萄糖浓度的穆勒细胞中的乳酸脱氢酶活性和肿瘤坏死因子-α mRNA表达显著降低。此外，胍丁胺处理抑制了葡萄糖诱导的穆勒细胞凋亡，这与Bax和Bcl-2表达的调节有关。胍丁胺处理抑制了葡萄糖诱导的穆勒细胞中丝裂原活化蛋白激酶（MAPK）蛋白的磷酸化。本研究表明，胍丁胺对穆勒细胞的保护作用被N-甲基-D-天冬氨酸（NMDA）抑制。本研究结果表明，胍丁胺处理可保护穆勒细胞免受高浓度葡萄糖诱导的细胞损伤。潜在机制可能与胍丁胺的抗炎和抗凋亡作用有关，以及通过抑制NMDA受体对MAPK途径的抑制作用有关。胍丁胺可能在开发糖尿病视网膜病变患者的新型治疗方法中有用。
