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中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (4): 436-439.

• 研究原著 • 上一篇    下一篇

扎鲁司特对大鼠局灶性脑缺血再灌注损伤的保护作用

刘颖, 余涓1, 许琳1, 陈崇宏   

  1. 福建医科大学药学院药理学系;1基础医学院生理学与病理生理学系, 福州350004, 福建
  • 收稿日期:2006-02-22 修回日期:2006-03-17 出版日期:2006-04-26 发布日期:2020-12-08
  • 通讯作者: 余涓, 女, 副教授, 硕士生导师, 研究方向:脑血管疾病的基础研究。Tel:0591-83574266  E-mail:fyjuanjuan@sina.com
  • 作者简介:刘颖, 女, 硕士, 研究方向:神经药理。Tel:0591-87353021  E-mail:xiaoying19762003@sina.com

Protective effects of zafirlukast on focal cerebral ischemia-reperfusion injury in rats

LIU Ying, YU Juan1, XU Lin1, CHEN Chong-hong   

  1. Department of Pharmacology, Pharmacy College, Fujian Medical University, Fuzhou 350004, Fujian, China;
    1Department of Physiology and Pathophysiology, Fujian Medical University, Fuzhou, 350004 Fujian, China
  • Received:2006-02-22 Revised:2006-03-17 Online:2006-04-26 Published:2020-12-08

摘要: 目的:探讨白三烯受体拮抗剂扎鲁司特对大鼠局灶性脑缺血再灌注损伤的保护作用及机制。方法:线栓法制备大鼠大脑中动脉缺血2 h 再灌注24 h 模型, 观察扎鲁司特(20 、40 mg·kg-1, 灌胃) 对脑梗死体积、脑水肿程度、血脑屏障通透性的影响,测定脑组织中髓过氧化物酶(MPO) 、丙二醛(MDA) 、谷胱甘肽过氧化物酶(GSH-PX) 、一氧化氮(NO) 及诱导型一氧化氮合酶(iNOS) 含量。结果:扎鲁司特能有效减少脑梗死体积、脑水肿程度与血脑屏障通透性, 增高脑组织GSH-PX 活性, 降低MDA 、MPO 含量,抑制iNOS 活性并减少NO 含量。结论:扎鲁司特对脑缺血再灌注损伤有保护作用, 其机制可能与降低血脑屏障通透性、抑制脑内炎症反应、抗脂质过氧化、降低NO 毒性有关。

关键词: 扎鲁司特, 再灌注损伤, 血脑屏障, 炎症反应, 脂质过氧化

Abstract: AIM: To study the protective effects of a leukotriene receptor antagonist zafirlukast on focal cerebral ischemia reperfusion injury (CIRI) in rats and its possible mechanisms.METHODS: Reversible middle cerebral artery occlusion(MCAO) model was produced by intraluminal suture technique, and reperfusion was begun after 2 h of occlusion.Zafirlukast was intragastrically administrated at 0 and 12 h of the reperfusion.After 24 h reperfusion the infarct volume of the brain, the cerebral edema degree and the permeability of blood brain barrier were estimated.The activity of myeloperoxidase (MPO), the contents of maleic dialdehyde (MDA), glutathione peroxidase (GSH-PX), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in the brain tissue were measured. RESULTS: Zafirlukast could decrease the infarct volume of the brain, lessen the degree of cerebral edema and reduce permeability of blood brain barrier.It could also decrease the content of MDA, the level of NO, the activity of iNOS and increase the activity of GSH-PX in the brain tissue significantly.The 40 mg·kg -1 dose of zafirlukast could reduce the activity of MPO.CONCLUSION: The highly selective leukotriene receptor antagonist zafirlukast can prevent cerebral ischemia reperfusion injury by depressing permeability of the blood brain barrier, inhibiting inflammation reaction, decreaseing lipid peroxidation and reducing toxic action of NO.

Key words: zafirlukast, reperfusion injury, blood brain barrier, inflammation, lipid peroxidation

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