Ginkgolide K promotes angiogenesis in a middle cerebral artery occlusion mouse model via activating JAK2/STAT3 pathway
Ginkgolide K promotes angiogenesis in a middle cerebral artery occlusion mouse model via activating JAK2/STAT3 pathway
复制标题
银杏内酯K通过激活JAK2/STAT3通路促进大脑中动脉闭塞小鼠模型血管生成
DOI：
10.1016/j.ejphar.2018.06.012
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发表时间：
2018-08-15
影响因子：
5
通讯作者：
Hu, Gang
中科院分区：
文献类型：
--
作者：
Chen, Meng;Zou, Wenyan;Hu, Gang
银杏内酯K（GK）是从银杏叶中提取的一种新化合物，具有抗氧化应激和神经保护作用。但它是否能促进缺血性脑卒中的血管生成尚不清楚。本研究旨在探讨银杏内酯K促进脑缺血再灌注后血管生成的作用及其保护机制。使用短暂性大脑中动脉闭塞（tMCAO）小鼠模型，我们发现GK（3.5，7.0，14.0 mg/kg，i. p.，出价，2周）减轻小鼠脑缺血再灌注14天后损伤的同侧皮质和纹状体的神经损伤，并促进血管生成。此外，GK（3.5 mg/kg in vivo，10 μ M in vitro）显著上调了OGD/R后tMCAO小鼠脑和B End 3细胞中HIF-1 α和VEGF的表达，并且GK诱导的B End 3细胞中HIF-1 α和VEGF的上调可被JAK 2/STAT 3抑制剂AG 490消除。我们的研究结果表明，GK通过JAK 2/STAT 3通路促进HIF-1 α/VEGF的表达，从而促进缺血性脑卒中后血管新生，为GK及其类似物在缺血性脑卒中治疗中的临床应用提供了新的思路。
Ginkgolide K (GK) is a new compound extracted from the leaves of Ginkgo biloba, which has been recognized to exert anti-oxidative stress and neuroprotective effect on ischemic stroke. While whether it plays an enhanced effect on angiogenesis during ischemic stroke remains unknown. The aim of this study was to investigate the effect of ginkgolide K on promoting angiogenesis as well as the protective mechanism after cerebral ischemia-reperfusion. Using the transient middle cerebral artery occlusion (tMCAO) mouse model, we found that GK (3.5, 7.0, 14.0 mg/kg, i.p., bid., 2 weeks) attenuated neurological impairments, and promoted angiogenesis of injured ipsilateral cortex and striatum after 14 days of cerebral ischemia-reperfusion in mice. Further, GK (3.5 mg/kg in vivo, 10 mu M in vitro) significantly up-regulated the expressions of HIF-1 alpha and VEGF in tMCAO mouse brains and in b End3 cells after OGD/R, and GK-induced upregulation of HIF-1 alpha and VEGF in b End3 cells could be abolished by JAK2/STAT3 inhibitor AG490. Our results demonstrate that GK promotes angiogenesis after ischemia stroke through increasing the expression of HIF-1 alpha/VEGF via JAK2/STAT3 pathway, which provide an insight into the novel clinical application of GK and its analogs in ischemic stroke therapy in future.