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中国药学(英文版) ›› 2016, Vol. 25 ›› Issue (12): 882-891.DOI: 10.5246/jcps.2016.12.099

• 【研究论文】 • 上一篇    下一篇

口服和厚朴酚对大鼠脑缺血再灌注(I-R)损伤和SHRsp脑卒中的保护作用

刘晓岩1, 胡振宇1, 陈世忠2, 王坚成3, 王银叶1*   

  1. 1. 北京大学医学部 药学院 分子与细胞药理学系, 北京 100191
    2. 北京大学医学部 药学院 天然药物学系, 北京 100191
    3. 北京大学医学部 药学院 药剂学系, 北京 100191
  • 收稿日期:2016-10-19 修回日期:2016-11-14 出版日期:2016-12-21 发布日期:2016-11-30
  • 通讯作者: Tel.: +86-010-82802652, E-mail: wangyinye@bjmu.edu.cn
  • 基金资助:
    National Natural Science Foundation of China (Grant No. 81503060).

Protective effects of orally administered honokiol on cerebral ischemia reperfusion in rats and on stroke in SHRsp

Xiaoyan Liu1, Zhenyu Hu1, Shizhong Chen2, Jiancheng Wang3, Yinye Wang1*   

  1. 1. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China
    2. Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, 100191, China
    3. Department of Pharmaceutics, School of Pharmaceutical Science, Peking University Health Science Center, Beijing, 100191, China
  • Received:2016-10-19 Revised:2016-11-14 Online:2016-12-21 Published:2016-11-30
  • Contact: Tel.: +86-010-82802652, E-mail: wangyinye@bjmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China (Grant No. 81503060).

摘要:

厚朴酚静脉注射对脑缺血再灌注损伤有保护作用, 本研究采用大鼠脑缺血再灌注损伤和自发性高血压易卒中(SHRsp)模型观察口服和厚朴酚微乳对大鼠脑卒中的保护作用。用血管收缩实验、原代大鼠主动脉内皮细胞和原代大鼠脑微血管内皮细胞损伤模型进一步探讨其作用机制。研究结果显示: 口服和厚朴酚微乳可明显减小I-R大鼠的脑梗死体积和神经行为学评分, 并降低脑组织水含量。该制剂也明显减小SHRsp卒中大鼠的神经行为学评分, 显著增加存活率。和厚朴酚明显抑制KCl和苯肾上腺素诱导的大鼠主动脉收缩反应, 增加大鼠主动脉内皮细胞NO的释放; NO合成酶抑制剂L-NAME可减弱和厚朴酚对血管收缩的抑制作用。和厚朴酚可增加大鼠主动脉内皮细胞p-eNOS水平和NO的释放。在缺糖缺氧/复糖复氧(OGD)损伤的大鼠脑微血管内皮细胞, 和厚朴酚明显增加细胞存活率, 增加eNOSp-eNOS的水平。这些结果提示: 和厚朴酚微乳口服对大鼠脑缺血再灌注(I-R)损伤和SHRsp 脑卒中具有明显保护作用, 这些作用与其内皮细胞保护作用和促进eNOS表达与活化有关。

关键词: 口服和厚朴酚, 脑缺血再灌注, SHRsp, 血管舒张, eNOS

Abstract:

Honokiol is a protective agent for cerebral ischemia injury when administered intravenously. In the present study, we aimed to investigate the oral effect of honokiol microemulsion on cerebral ischemia-reperfusion (I-R) injury in rats and stroke in SHRsp. Both tMCAO and SHRsp models in rats were used to evaluate the efficacy of the microemulsion. Rat aortic segment contraction test, primary rat aortic endothelial cells and primary brain microvascular endothelial cells (BMECs) injured by OGD-R were used to explore its potential action mechanism. Oral honokiol microemulsion significantly reduced infarct volume, neurological score and brain water content in tMCAO model, and it evidently reduced neurological score and increased the survival rate of SHRsp. Moreover, honokiol significantly inhibited aortic contraction induced by KCl and phenylephrine, and L-NAME suppressed these inhibitory effects. On the other side, honokiol increased NO and p-eNOS levels in rat endothelial cells. In addition, it also protects BMECs against OGD-R injury and increased eNOS expression in BMECs. In conclusion, oral honokiol administration has protective effects in tMCAO and in SHRsp rats, and its action mechanism is likely to be associated with its vasodilative effect produced by eNOS activation and with its protective effect on BMECs.  

Key words: Honokiol, Cerebral ischemia-reperfusion, SHRsp, Vasodilatory, eNOS

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