中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (28): 2625-2632.doi: 10.3969/j.issn.1673-5374.2013.28.004

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

柿叶黄酮如何提高脑缺血的耐受性?

  

  • 收稿日期:2013-02-05 修回日期:2013-06-08 出版日期:2013-10-05 发布日期:2013-10-05

Persimmon leaf flavonoid promotes brain ischemic tolerance

Mingsan Miao, Xuexia Zhang, Ming Bai, Linan Wang   

  1. Henan University of Traditional Chinese Medicine, Zhengzhou 450008, Henan Province, China
  • Received:2013-02-05 Revised:2013-06-08 Online:2013-10-05 Published:2013-10-05
  • Contact: Mingsan Miao, M.D., Professor, Henan University of Traditional Chinese Medicine, Zhengzhou 450008, Henan Province, China, miaomingsan@ 163.com.

摘要:

课题组的前期研究发现柿叶黄酮可增强小鼠的脑缺血耐受作用,但相关机制尚不清楚。采用微动脉夹夹闭大鼠双侧颈总动脉10min后再灌注的方法对大鼠进行缺血预处理诱导脑缺血耐受,之后每天灌胃给予200,100,50mg/kg柿叶黄酮或20mg/kg金纳多连续5d进行药物干预。末次给药后1 h阻断大鼠大脑中动脉2h进行再灌注制备脑缺血再灌注模型。造模后24h,与未进行缺血预处理及药物干预的脑缺血大鼠比较,缺血预处理的大鼠血浆内皮素、血栓调节素及假性血友病因子水平明显降低,脑组织细胞间黏附分子1表达明显减少,同时脑组织损伤相对减轻。缺血预处理与药物联合对以上指标的改善作用更明显,以200mg/kg柿叶黄酮和金纳多的作用最佳。说明缺血预处理可以对再次发生的严重脑缺血产生耐受性,而柿叶黄酮可通过减轻炎症反应,减少血管内皮损伤提高脑缺血耐受大鼠的耐缺血作用,其中大剂量柿叶黄酮与金纳多的作用相当。

关键词: 神经再生, 中医药, 柿叶黄酮, 脑损伤, 脑缺血耐受, 缺血预处理, 金纳多, 缺血再灌注损伤, 细胞间黏附分子1, 内皮素

Abstract:

Persimmon leaf flavonoid has been shown to enhance brain ischemic tolerance in mice, but its mechanism of action remains unclear. The bilateral common carotid arteries were occluded using a micro clip to block blood flow for 10 minutes. After 10 minutes of ischemic preconditioning, 200, 100, and 50 mg/kg persimmon leaf flavonoid or 20 mg/kg ginaton was intragastrically administered per day for 5 days. At 1 hour after the final administration, ischemia/reperfusion models were estab-lished by blocking the middle cerebral artery for 2 hours. At 24 hours after model establishment, compared with cerebral ischemic rats without ischemic preconditioning or drug intervention, plasma endothelin, thrombomodulin and von Willebrand factor levels significantly decreased and intercel-lular adhesion molecule-1 expression markedly reduced in brain tissue from rats with ischemic pre-conditioning. Simultaneously, brain tissue injury reduced. Ischemic preconditioning combined with drug exposure noticeably improved the effects of the above-mentioned indices, and the effects of 200 mg/kg persimmon leaf flavonoid were similar to 20 mg/kg ginaton treatment. These results indicate that ischemic preconditioning produces tolerance to recurrent severe cerebral ischemia. However, persimmon leaf flavonoid can elevate ischemic tolerance by reducing inflammatory reactions and vascular endothelial injury. High-dose persimmon leaf flavonoid showed an identical effect to ginaton.

Key words: neural regeneration, traditional Chinese medicine, persimmon leaf flavonoid, brain injury, brain is-chemic tolerance, ischemic preconditioning, ginaton, ischemia/reperfusion injury, intercellular ad-hesion molecule-1, endothelin, grants-supported paper, neuroregeneration