Curcumin protects against stroke and increases levels of Notch intracellular domain

Curcumin protects against stroke and increases levels of Notch intracellular domain
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DOI:
10.1080/01616412.2016.1187804
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发表时间:
2016-01-01
影响因子:
1.9
通讯作者:
Han, Zhao
Han, Zhao
中科院分区:
医学4区
文献类型:
--
作者:
Liu, Shuang;Cao, Yungang;Han, Zhao

文献摘要

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目的:探讨姜黄素是否通过调节Notch信号通路引起局灶性缺血再灌注损伤后的神经保护和神经发生。方法:通过阻断大脑中动脉建立大鼠局灶性缺血再灌注损伤模型。这些动物在中风后 1 小时开始腹腔注射姜黄素 (300 mg/kg) 或玉米油(媒介物),持续 7 天。同时,假手术对照动物接受载体。所有动物在第 12 天处死。使用免疫组织化学、免疫荧光和蛋白质印迹比较不同治疗组的神经行为缺陷、BrdU 掺入以及双皮质素 (DCX) 和 Notch 胞内结构域 (NICD) 水平。结果:再灌注 3、7 和 12 天后,用姜黄素治疗的动物表现出比载体治疗的动物显着更小的神经行为缺陷(所有 p < 0.05)。姜黄素处理动物的组织切片中含有显着更多数量的 BrdU 阳性细胞 (p < 0.05) 和 BrdU/DCX 阳性细胞 (p < 0.01),以及显着更高的 NICD 水平 (p < 0.01)。结论:姜黄素可以保护免受局灶性脑缺血再灌注损伤,并通过激活 Notch 信号通路刺激神经发生。
Objectives: To investigate whether curcumin regulates Notch signaling to cause neuroprotection and neurogenesis after focal ischemia reperfusion injury.Method: Focal ischemia reperfusion injury was modeled in rats by occluding the middle cerebral artery. These animals were given either curcumin (300 mg/kg) or corn oil (vehicle) by intraperitoneal injection starting 1 h after stroke and continuing for 7 d. In parallel, sham-operated control animals received vehicle. All animals were killed on day 12. The different treatment groups were compared in terms of neurobehavioral deficits, BrdU incorporation, and levels of doublecortin (DCX) and Notch intracellular domain (NICD) using immunohistochemistry, immunofluorescence and Western blotting.Results: Animals treated with curcumin showed significantly smaller neurobehavioral deficits than vehicle-treated animals after 3, 7, and 12 d of reperfusion (all p < 0.05). Tissue sections from curcumin-treated animals contained significantly greater numbers of BrdU-positive cells (p < 0.05) and BrdU/DCX-positive cells (p < 0.01), as well as significantly higher NICD levels (p < 0.01).Conclusion: Curcumin may protect from focal cerebral ischemia reperfusion injury as well as stimulate neurogenesis by activating the Notch signaling pathway.