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。
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 zatirlukast can prevent cerebral isehemia reperfusion injury by depressing permeability of the blood brain barrier, inhibiting inflammation reaction, decreaseing lipid peroxidation and reducing toxic action of NO.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2006年第4期436-439,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
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
zafirlukast
reperfusion injury
blood brain barrier
inflammation
lipid peroxidation
