5-脂氧酶在全脑缺血海马CA1神经元损伤中的作用  

Expression of 5-lipoxygenase in hippocampal CA1 neuronal damage following global cerebral ischemia in rats

作　　者：陈文健[1] 李成檀[1] 赵建波[1] 张晓燕[1] 韩华阳[1] 魏尔清[2] 张丽慧[1] 

机构地区：[1]杭州师范大学医学神经生物学市级重点实验室,基础医学部药理学教研室,浙江杭州310036 [2]浙江大学医学院药理学系,浙江杭州310058

出　　处：《浙江大学学报（医学版）》2013年第1期61-66,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：浙江省自然科学基金资助项目(Y204210,LY12H31010);杭州市科技计划项目(20080333B21);杭州市重点实验室项目(20090233T12)

摘　　要：目的:观察全脑缺血后海马神经元损伤中5-脂氧酶(5-LOX)的表达变化,并探讨5-LOX选择性抑制剂zileuton对全脑缺血海马神经元损伤的保护作用。方法:在双侧颈总动脉阻断结合降压药诱导大鼠全脑缺血模型,Western blot方法检测脑缺血损伤中5-LOX的表达改变;免疫组织化学及免疫荧光双标染色方法观察5-LOX的分布特征。应用5-LOX选择性抑制剂zileuton(10、30、50 mg/kg,缺血前后2 h灌胃给药,以后每日2次,共3 d)观察脑缺血后海马神经元的损伤变化。结果:大鼠全脑缺血后3～14 d,海马CA1神经元产生迟发性神经元死亡;海马5-LOX表达在全脑缺血后1～7 d增高,并于3 d达高峰;在海马CA1区,5-LOX主要表达在神经元胞浆,脑缺血后5-LOX发生核移位现象。5-LOX抑制剂zileuton(30和50 mg/kg)能减少全脑缺血后海马CA1神经元的死亡。结论:5-LOX参与大鼠全脑缺血诱导的海马神经元损伤,5-LOX抑制剂zileuton对全脑缺血海马神经元损伤有保护作用。Objective： To determine 5-lipoxygenase （5-LOX） expression and the effect of zileuton, a selective 5-LOX inhibitor, on hippocampal neuron injury induced by global cerebral ischemia in rats. Methods： Global cerebral ischemia was induced by bilateral common carotid artery occlusion combined with hypotension in rats. 5-LOX expression was detected by Western blot analyses and 5-LOX localization was visualized by immunohistochemistry and double immunofluorescence methods. The 5-LOX inhibitor zileuton （10,30,50 mg/kg） was orally administered for 3 d after ischemia. Results： The 5-LOX expression was increased in the primarily localized in neurons ischemic hippocampus on dl-7 （ and translocated to the nuclei peaked at d3）, and 5-LOX protein was in the hippocampal CA1 region after ischemia. The 5-LOX inhibitor zileuton （30,50 mg/kg） reduced ischemia-induced hippocampal neurons death 3d after ischemia. Conclusions： 5-LOX is involved in global cerebral ischemic damage in rats, and the 5-LOX inhibitor zileuton has a protective effect on neuronal damage in the rat hippocampus following global cerebral ischemia.

关 键 词：羟基脲/治疗应用 脂氧合酶抑制剂/药理学 脑缺血/药物疗法 海马/细胞学 神经元/细胞学 疾病模型 动物 

分 类 号：R743[医药卫生—神经病学与精神病学]