Epigallocatechin-3-gallate promotes angiogenesis via up-regulation of Nfr2 signaling pathway in a mouse model of ischemic stroke

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• 作者：Qian Bai^a ; ¹ ; Zhipai Lyu^b ; ¹ ; Xianhui Yang^a ; ¹ ; Zhenjie Pan^c ; Jiyu Lou^d ; ^{drloujy@163.com} ; Tieli Dong^a ; ^{drdongtl@yeah.net}
• 关键词：Ischemic stroke ; EGCG ; Nrf2 ; Angiogenesis
• 刊名：Behavioural Brain Research
• 出版年：2017
• 出版时间：15 March 2017
• 年：2017
• 卷：321
• 期：Complete
• 页码：79-86
• 全文大小：3409 K
• 卷排序：321

文摘

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.