Trans-Chalcone prevents VEGF expression and retinal neovascularization in the ischemic retina
Trans-Chalcone prevents VEGF expression and retinal neovascularization in the ischemic retina
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DOI：
10.1016/j.exer.2011.02.007
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发表时间：
2011-10-01
影响因子：
3.4
通讯作者：
Bartoli, Manuela
中科院分区：
文献类型：
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作者：
Lamoke, Folami;Labazi, Mohamed;Bartoli, Manuela
视网膜新生血管(RNV)是一种重要的病理事件，也是致盲的主要原因。血管炎症和氧化应激在RNV的诱导和发展中起关键作用。反式查尔酮衍生的黄酮类化合物此前已被证明是氧化应激、炎症反应以及肿瘤血管生成的负调控因子。在这项研究中，我们研究了黄酮类反式查尔酮在预防缺血性视网膜病变模型中的RNV的作用。在新生小鼠氧诱导视网膜病变的基础上，建立了缺血性视网膜病变模型。反式查尔酮按25 mg/kg/d腹腔注射。血管密度通过形态计量学分析德州红-Isolectin B4染色的平板型视网膜来评估。Western blotting检测血管内皮生长因子(VEGF)、细胞间黏附分子-1(ICAM-1)、转录激活物信号转导和激活因子3(STAT3)、核因子-kappaB(NF-kappa B)的蛋白水平。反式查尔酮治疗可显著抑制缺血视网膜中的RNV，表现为新生血管数量减少。反式查尔酮还可阻断缺血诱导的血管内皮生长因子和细胞间黏附分子-1的表达，这种作用与抑制活化的STAT3和核因子-kappaB有关。我们的结果表明，反式查尔酮有效地阻止了小鼠视网膜的RNV，提示查尔酮衍生的黄酮类化合物可能有助于防止缺血视网膜的病理性新生血管。爱思唯尔有限公司出版。
Retinal neovascularization (RNV) is a critical pathological event and a major cause of blindness. Vascular inflammation and oxidative stress have been shown to play a key role in the induction and progression of RNV. Trans-Chalcone-derived flavonoids have been previously shown to be negative modulators of oxidative stress and inflammatory responses as well as tumor angiogenesis. In this study, we characterized the effects of the flavonoid trans-Chalcone in preventing RNV in a model of ischemic retinopathy. Ischemic retinopathy was induced in neonatal mice subjected to oxygen-induced retinopathy. Trans-Chalcone was administered intra-peritoneum at the dose of 25 mg/kg/day. Vascular density was assessed by morphometric analysis of flat mounted retinas stained with Texas red-Isolectin B4. Western blotting analysis was conducted to determine protein levels of vascular endothelial growth factor (VEGF), inter-cellular adhesion molecule 1 (ICAM-1) and the transcriptional activators' signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa beta (NF-kappa B). Treatment with trans-Chalcone significantly inhibited RNV in the ischemic retina, as shown by decreased number of neovascular tufts. Trans-Chalcone also blocked ischemia-induced VEGF and ICAM-1 expression and this effect correlated with inhibition of activated STAT3 and NF-kappa B. Our results show that trans-Chalcone effectively prevents RNV in the murine retina thus suggesting that Chalcone-derived flavonoids may be beneficial in preventing pathological neovascularization in the ischemic retina. Published by Elsevier Ltd.