Epigallocatechin-3-gallate promotes angiogenesis via up-regulation of Nfr2 signaling pathway in a mouse model of ischemic stroke
Epigallocatechin-3-gallate promotes angiogenesis via up-regulation of Nfr2 signaling pathway in a mouse model of ischemic stroke
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DOI：
10.1016/j.bbr.2016.12.037
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发表时间：
2017-03-15
影响因子：
2.7
通讯作者：
Dong, Tieli
中科院分区：
文献类型：
--
作者：
Bai, Qian;Lyu, Zhipai;Dong, Tieli
表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶的主要有效成分，因其抗氧化和抗血管生成特性而被称为潜在的抗癌药物。据报道，EGCG 通过核因子红细胞 2 相关因子 2 (Nfr2) 信号通路对缺血性中风具有预防作用，但 EGCG 如何影响中风后血管生成仍不清楚。在这项研究中，我们研究了缺血性中风急性期的 EGCG 治疗是否可以促进暂时性大脑中动脉闭塞 (MCAO) 小鼠模型的血管生成。我们通过改良的神经系统严重程度评分（mNSS）测试评估神经功能，通过Nessl染色评估梗塞体积，通过免疫荧光分析、活体凝集素灌注分析、蛋白质印迹分析和酶联免疫吸附测定（ELISA）评估血管生成和氧化应激。为了探讨Nrf2在MCAO+EGCG处理的小鼠血管生成中的作用，我们使用MAPK/ERK抑制剂PD98059来阻断Nrf2的激活。我们发现，与 MCAO + 载体治疗的小鼠相比，MCAO + EGCG 治疗的小鼠具有更好的神经系统结果、更小的梗塞体积、更多的 Ki67/CD31 阳性血管、更高的血管密度、不受调节的 VEGF-VEGFR2 信号通路、增加的 Nrf2 表达和减少的氧化应激。用 PD98059 阻断 Nrf2 显着降低 Nrf2 的表达，增加氧化应激，并消除 EGCG 对 MCAO 小鼠的血管生成和神经保护作用。我们得出的结论是，缺血性中风早期的 EGCG 治疗可以促进 MCAO 小鼠的血管生成，可能是通过上调 Nrf2 信号通路来实现的。 (C) 2016 Elsevier B.V. 保留所有权利。
Epigallocatechin-3-gallate (EGCG) is the major effective component of green tea and has been known as a potential anticancer drug because of its antioxidant and anti-angiogenic properties. EGCG has also been reported to have preventive effects against ischemic stroke via nuclear factor erythroid 2-related factor 2 (Nfr2) signaling pathway, but how EGCG affect angiogenesis after stroke remains unclear. In this study, we investigated whether EGCG treatment in the acute phase of ischemic stroke can promote angiogenesis in a mouse model of transient middle cerebral artery occlusion (MCAO). We assessed neurological function with modified neurologic severity score (mNSS) test, infarct volume by Nessl staining, angiogenesis and oxidative stress by immunofluorescence analysis, intravital lectin perfusion analysis, western blot analysis and enzyme-linked immunosorbent assay (ELISA). In order to explore the role of Nrf2 in the angiogenesis of MCAO + EGCG-treated mice, we used MAPK/ERK inhibitor PD98059 to block the activation of Nrf2. We found MCAO + EGCG-treated mice had better neurologic outcome, less infarct volume, more number of Ki67/CD31-positive vessels, higher vascular density, unregulated VEGF-VEGFR2 signaling pathway, increased Nrf2 expression and decreased oxidative stress than did MCAO + vehicle-treated mice. Blocking Nrf2 with PD98059 significantly reduced the expression of Nrf2, increased oxidative stress and abolished the angiogenic and neuroprotective effects of EGCG on MCAO mice. We conclude that EGCG treatment in the early stage of ischemic stroke can promote angiogenesis in MCAO mice, possibly via upregulation of Nrf2 signaling pathway. (C) 2016 Elsevier B.V. All rights reserved.