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内皮抑素在视网膜新生血管小鼠模型中对血管内皮生长因子和整合素β3的下调作用

Downregulation of vascular endothelial growth factor and integrinbeta3 by endostatin in a mouse model of retinal neovascularization.

作者信息

Zhang Meixia, Yang Yang, Yan Mi, Zhang Junjun

机构信息

West China Eye Center, West China Hospital, Sichuan University, 37 Guoxuexiang, Chengdu, Sichuan Province 610041, China.

出版信息

Exp Eye Res. 2006 Jan;82(1):74-80. doi: 10.1016/j.exer.2005.05.005. Epub 2005 Sep 29.

DOI:10.1016/j.exer.2005.05.005
PMID:16198337
Abstract

Retinal neovascularization is among the leading causes of vision impairment throughout the world. Intraocular expression of vascular endothelial growth factor (VEGF), an angiogenic protein, and integrins, a group of cell adhesion molecules, is closely correlated with neovascularization in such neovascular diseases. The purpose of this study is to determine the effect of endostatin, a potent anti-angiogenic factor, on gene expression of vascular endothelial growth factor (VEGF) and integrinbeta3 in a mouse model of oxygen-induced retinopathy. C57BL/6 mice were given intravitreous injections of 1.0 microg endostatin at P12. At P17, retinal VEGF and integrinbeta3 mRNA levels were measured by real-time quantitative PCR in the hyperoxia mice and in the endostatin-treated mice. Analysis of 12 separate experiments revealed a 3.5-fold decrease in VEGF levels between hyperoxia mice and endostatin-treated mice (p<0.01) and a 2.5-fold decrease in integrinbeta3 levels between hyperoxia mice and endostatin-treated mice (p<0.01). These data suggest that intraocular expression of VEGF and integrinbeta3 mRNA is down-regulated by endostatin, which may provide a new therapeutic approach for ocular neovascularization.

摘要

视网膜新生血管形成是全球视力损害的主要原因之一。血管内皮生长因子(VEGF,一种血管生成蛋白)和整合素(一组细胞粘附分子)的眼内表达与这类新生血管疾病中的新生血管形成密切相关。本研究的目的是在氧诱导性视网膜病变小鼠模型中确定内皮抑素(一种有效的抗血管生成因子)对血管内皮生长因子(VEGF)和整合素β3基因表达的影响。在出生后第12天给C57BL/6小鼠玻璃体内注射1.0微克内皮抑素。在出生后第17天,通过实时定量PCR测量高氧小鼠和内皮抑素治疗小鼠的视网膜VEGF和整合素β3 mRNA水平。对12个独立实验的分析显示,高氧小鼠和内皮抑素治疗小鼠之间VEGF水平降低了3.5倍(p<0.01),高氧小鼠和内皮抑素治疗小鼠之间整合素β3水平降低了2.5倍(p<0.01)。这些数据表明,内皮抑素可下调VEGF和整合素β3 mRNA的眼内表达,这可能为眼内新生血管形成提供一种新的治疗方法。

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