* School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
∥ Department of Chinese Medicine, Hui-Sheng Hospital, Taichung 42056, Taiwan.
Am J Chin Med. 2017;45(8):1683-1708. doi: 10.1142/S0192415X17500914. Epub 2017 Nov 9.
This study evaluated the effects of Angelica sinensis extract [Dang Gui (DG)] administered before 60[Formula: see text]min of middle cerebral artery occlusion followed by 3[Formula: see text]d of reperfusion and investigated the involvement of mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor (HIF)-1[Formula: see text] signaling in the cortical ischemic penumbra. DG was intraperitoneally administered at a dose of 0.25[Formula: see text]g/kg (DG-0.25g), 0.5[Formula: see text]g/kg (DG-0.5g), or 1[Formula: see text]g/kg (DG-1g) 30[Formula: see text]min before the onset of cerebral ischemia. Our study results revealed that DG-0.5g and DG-1g pretreatment effectively attenuated cerebral infarct and improved neurological deficits. DG-0.5g and DG-1g pretreatment significantly downregulated glial fibrillary acidic protein (GFAP), cytochrome c, and cleaved caspase-3 expression and upregulated phospho-p38 MAPK (p-p38 MAPK)/p38 MAPK, phospho-cAMP response element-binding protein (p-CREB)/CREB, cytosolic and mitochondrial phospho-Bad (p-Bad)/Bad ratios, and HIF-1[Formula: see text], vascular endothelial growth factor-A (VEGF-A), phospho-90 kDa ribosomal S6 kinase (p-p90RSK), and von Willebrand factor (vWF) expression in the cortical ischemic penumbra. Pretreatment with SB203580, a p38 MAPK inhibitor, dramatically abrogated the upregulating effects of DG-1g on p-p38 MAPK/p38 MAPK, p-CREB/CREB, and p-Bad/Bad ratios and HIF-1[Formula: see text], VEGF-A, and vWF expression and the downregulating effects of DG-1g on GFAP, cytochrome c, cleaved caspase-3, and cerebral infarction. DG-0.5g and DG-1g pretreatment provided neuroprotective effects against astrocyte-mediated cerebral infarction by activating angiogenic and anti-apoptotic signaling. Moreover, the angiogenic and anti-apoptotic effects of DG pretreatment can be attributed to the activation of p38 MAPK/HIF-1[Formula: see text]/VEGF-A/vWF signaling and p38 MAPK/HIF-1[Formula: see text]/VEGF-A/p-Bad-related regulation of cytochrome c/caspase-3 signaling, respectively, in the cortical ischemic penumbra 3[Formula: see text]d after reperfusion.
本研究评价了当归提取物（当归）在大脑中动脉闭塞 60[Formula: see text]min 前给药，随后再灌注 3[Formula: see text]d 的效果，并研究了丝裂原活化蛋白激酶（MAPK）/缺氧诱导因子（HIF）-1[Formula: see text]信号在皮质缺血半影区中的作用。DG 以 0.25[Formula: see text]g/kg（DG-0.25g）、0.5[Formula: see text]g/kg（DG-0.5g）或 1[Formula: see text]g/kg（DG-1g）的剂量腹腔内给药，在脑缺血发作前 30[Formula: see text]min 给药。我们的研究结果表明，DG-0.5g 和 DG-1g 预处理可有效减轻脑梗死和改善神经功能缺损。DG-0.5g 和 DG-1g 预处理可显著下调胶质纤维酸性蛋白（GFAP）、细胞色素 c 和 cleaved caspase-3 的表达，并上调磷酸化 p38 MAPK（p-p38 MAPK）/p38 MAPK、磷酸化 cAMP 反应元件结合蛋白（p-CREB）/CREB、胞浆和线粒体磷酸化 Bad（p-Bad）/Bad 比值以及 HIF-1[Formula: see text]、血管内皮生长因子-A（VEGF-A）、磷酸化 90 kDa 核糖体 S6 激酶（p-p90RSK）和血管性假血友病因子（vWF）在皮质缺血半影区的表达。p38 MAPK 抑制剂 SB203580 预处理可显著阻断 DG-1g 对 p-p38 MAPK/p38 MAPK、p-CREB/CREB 和 p-Bad/Bad 比值及 HIF-1[Formula: see text]、VEGF-A 和 vWF 表达的上调作用，以及 DG-1g 对 GFAP、细胞色素 c、cleaved caspase-3 和脑梗死的下调作用。DG-0.5g 和 DG-1g 预处理通过激活血管生成和抗细胞凋亡信号，对星形胶质细胞介导的脑梗死具有神经保护作用。此外，DG 预处理的血管生成和抗细胞凋亡作用可能归因于 p38 MAPK/HIF-1[Formula: see text]/VEGF-A/vWF 信号的激活以及 p38 MAPK/HIF-1[Formula: see text]/VEGF-A/p-Bad 相关的细胞色素 c/caspase-3 信号的调节，分别在再灌注后 3[Formula: see text]d 在皮质缺血半影区。
