Mu Ying, Xu Zhaohui, Zhou Xuanxuan, Zhang Huinan, Yang Qian, Zhang Yunlong, Xie Yanhua, Kang Juan, Li Feng, Wang Siwang
Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xian, People's Republic of China.
323th Hospital of PLA, Xian, People's Republic of China.
Planta Med. 2017 May;83(8):676-683. doi: 10.1055/s-0042-120544. Epub 2016 Nov 28.
Cerebral ischemia can cause brain infarcts, which are difficult to recover due to poor angiogenesis. 2,3,5,4'-Tetrahydroxystilbene-2-O--D-glucoside is a natural polyphenol, has antioxidant and anti-inflammatory activity, and can protect from ischemic neuronal injury. However, little is known about the effect of 2,3,5,4'-tetrahydroxystilbene-2-O--D-glucoside on brain microcirculation after stroke. This study aimed at investigating the influence of 2,3,5,4'-tetrahydroxystilbene-2-O--D-glucoside on brain lesions and angiogenesis after stroke. Sprague-Dawley rats were subjected to right middle cerebral artery occlusion and treated with vehicle, nimodipine, or different doses of 2,3,5,4'-tetrahydroxystilbene-2-O--D-glucoside daily beginning at 6 h post-middle cerebral artery occlusion for 14 days. The volume of cerebral infarcts, degree of neurological dysfunction, and level of microvessel density were determined longitudinally. The levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions were characterized by immunohistochemistry and Western blot assays at 14 days post-middle cerebral artery occlusion. We found that 2,3,5,4'-tetrahydroxystilbene-2-O--D-glucoside significantly promoted postoperative recovery in rats by minimizing the volume of cerebral infarcts and improving neurological dysfunction in a dose- and time-dependent manner. Additionally, 2,3,5,4'-tetrahydroxystilbene-2-O--D-glucoside significantly increased the microvessel density in the brain and upregulated CD31 expression in ischemic penumbra, relative to that in the control. Finally, treatment with 2,3,5,4'-tetrahydroxystilbene-2-O--D-glucoside significantly upregulated the relative levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions of rats. Therefore, these data indicated that 2,3,5,4'-tetrahydroxystilbene-2-O--D-glucoside treatment promoted angiogenesis and recovery from ischemia/reperfusion-induced brain injury in rats.
脑缺血可导致脑梗死，由于血管生成不良，脑梗死难以恢复。2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷是一种天然多酚，具有抗氧化和抗炎活性，可保护神经元免受缺血性损伤。然而，关于2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷对中风后脑微循环的影响知之甚少。本研究旨在探讨2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷对中风后脑损伤和血管生成的影响。将Sprague-Dawley大鼠进行右侧大脑中动脉闭塞，并在大脑中动脉闭塞后6小时开始每天用溶剂、尼莫地平或不同剂量的2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷治疗14天。纵向测定脑梗死体积、神经功能障碍程度和微血管密度水平。在大脑中动脉闭塞后14天，通过免疫组织化学和蛋白质印迹分析对脑损伤中血管内皮生长因子、血管生成素1和血管生成素受体-2的表达水平进行表征。我们发现，2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷通过以剂量和时间依赖性方式最小化脑梗死体积并改善神经功能障碍，显著促进了大鼠术后恢复。此外，相对于对照组，2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷显著增加了脑中的微血管密度，并上调了缺血半暗带中CD31的表达。最后，用2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷治疗显著上调了大鼠脑损伤中血管内皮生长因子、血管生成素1和血管生成素受体-2的相对表达水平。因此，这些数据表明，2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷治疗可促进大鼠血管生成并从缺血/再灌注诱导的脑损伤中恢复。
