紫杉醇通过MLK_3/JNK_3信号通路对海马神经元损伤的保护作用  

Effect and mechanism of paclitaxel on neuronal injury induced by cerebral ischemia/reperfusion through MLK_3/JNK_3 signaling pathway

作　　者：齐素华[1] 巩娟娟[1] 倪小宇[2] 

机构地区：[1]徐州医学院生物化学与分子生物学研究中心江苏省脑病信息研究中心,江苏徐州221002 [2]徐州医学院附属医院神经内科,江苏徐州221002

出　　处：《苏州大学学报（医学版）》2012年第1期1-5,共5页Suzhou University Journal of Medical Science

基　　金：国家自然科学基金(项目编号:81171075);江苏省教育厅自然科学基金(项目编号:08KJB180010;11KJB310012);徐州医学院人才基金(项目编号:2010KJZ13)

摘　　要：目的研究紫杉醇对脑缺血/再灌注后海马神经元损伤的保护作用的分子机制。方法采用SD大鼠四动脉结扎脑缺血模型(4-VO),在缺血前30 min脑室注射紫杉醇(4、8、12、20μg/kg),应用免疫沉淀及免疫印迹方法分析JNK3/MLK3/Fas-L的蛋白表达量和激活情况;焦油紫染色,观察紫杉醇对大鼠海马神经元的作用。结果紫杉醇显著抑制了脑缺血/再灌注后JNK3/MLK3/Fas-L的激活;焦油紫染色观察,紫杉醇对大鼠海马神经元的凋亡有明显的抑制作用。结论紫杉醇对脑缺血/再灌注诱导的海马神经元的损伤具有保护作用,这种保护作用和JNK3介导的信号通路密切相关,为临床治疗脑中风提供理论依据。Objective To study the effects and molecular mechanisms of paclitaxel （P） on the brain injury of hippocampal neurons induced by ischemia/reperfusion （ I/ R）. Methods Westen blot assay was used to examine the JNK3/MLK3 activation in the four-vessel occlusion （4-VO） model of Sprague- Dawley rats. And cresly violet staining was to demonstrate the survival of nerve cell in I/R. Results Transient cerebral ischemia followed by reperfusion caused a significant increase in phosphorylation of JNK3/MLK3/Fas-L. Administration of paclitaxel 30 rain before ischemia caused a pronounced decrease phosphorylation of JNK3/MLK3/Fas-L, but the administration of the vehicles DMSO had no effect. Cresyl violet staining showed that neurons in hippocampi subjected to paclitaxel （30 min before, Pre-ischemia 4 μg/kg, 8 μg/kg, 12μg/kg, 20μg/kg） were protected significantly compared with those without paclitaxel. Conclusion Paclitaxel has neuroprotective effect against I/R induced neuronal cell death and this effect correlated with JNK3 signaling pathway. These findings might provide some clues to understand the mechanism underlying ischemia tolerance and to finding clinical therapies for stroke.

关 键 词：紫杉醇 脑缺血/再灌注 JNK3(c-Jun N-TERMINAL kinase) MLK3(mixed LINEAGE kinase) FAS-L 

分 类 号：R743.31[医药卫生—神经病学与精神病学]