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TGF-β 抑制剂对 NMDA 诱导的视网膜变性大鼠模型的保护作用。

Protective effects of TGF-β inhibitors in a rat model of NMDA-induced retinal degeneration.

机构信息

Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.

出版信息

Eur J Pharmacol. 2013 Jan 15;699(1-3):188-93. doi: 10.1016/j.ejphar.2012.11.054. Epub 2012 Dec 7.

Abstract

Recent studies have shown that the retinal blood vessels are damaged in experimental models of retinal degeneration, but the mechanisms underlying their damage are not fully understood. In this study, we examined the possible role of transforming growth factor (TGF)-β in retinal neuron loss and capillary degeneration induced in rats by an intravitreal injection of N-methyl-d-aspartate (NMDA). The number of cells in the ganglion cell layer was significantly decreased 2 days after NMDA treatment, and a further decrease was observed at 7 days. Enhanced capillary degeneration was detected 7 days after NMDA treatment. Simultaneous injection of NMDA and the TGF-β inhibitor (SB431542 or LY364947) slightly but significantly attenuated the reduction in number of cells in the ganglion cell layer and almost completely prevented the enhancement of capillary degeneration. These results suggest that activation of the TGF-β signaling pathway induces neuronal and vascular cell damage in rat retina.

摘要

最近的研究表明,视网膜血管在视网膜变性的实验模型中受到损伤,但它们损伤的机制尚不完全清楚。在这项研究中,我们研究了转化生长因子(TGF)-β在大鼠眼内注射 N-甲基-D-天冬氨酸(NMDA)引起的视网膜神经元损失和毛细血管退化中的可能作用。NMDA 处理后 2 天,节细胞层中的细胞数量明显减少,7 天后进一步减少。NMDA 处理 7 天后检测到增强的毛细血管退化。同时注射 NMDA 和 TGF-β抑制剂(SB431542 或 LY364947)可轻微但显著减轻节细胞层细胞数量的减少,并几乎完全防止毛细血管退化的增强。这些结果表明,TGF-β信号通路的激活诱导大鼠视网膜神经元和血管细胞损伤。

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