凋亡诱导因子在实验性脑卒中后高温状态下的表达  

The Expression of Apoptosis-Inducing Factor in Vulnerable Neurons and PC12 Cultures After Experimental Postischemic Hyperthermia

作　　者：刘丽萍[1] 王拥军[1] 万虹[2] 历俊华[2] 翟晶[2] 王春雪[1] 毛淑静[3] 

机构地区：[1]首都医科大学附属北京天坛医院神经内科,北京100050 [2]北京神经外科研究所 [3]河北医科大学附属第二医院药剂科,石家庄150040

出　　处：《中国卒中杂志》2006年第9期619-623,共5页Chinese Journal of Stroke

摘　　要：目的探讨caspase非依赖途径在卒中后高温的神经元损伤环节中是否发挥重要作用。方法应用SD大鼠局灶性脑缺血模型,分别设立缺血后高温、缺血后正常温度和假手术组,每组8只。观察动物行为学评分、梗死体积和凋亡诱导因子(AIF)在海马的表达。利用PC12细胞培养缺氧及高温处理后,观察荧光双染AIF在细胞内的表达变化,及流式细胞仪技术检测细胞凋亡水平。结果缺血后高温组的行为学评分和梗死体积明显增加,AIF表达增高。PC12缺氧及高温培养后AIF从30min开始在胞核内表达,且随时间延长逐渐增多,细胞凋亡率随时间延长和温度增高而增加,且不被caspase广谱抑制剂所抑制。结论AIF在卒中后高温的过程中发生由胞浆到胞核的转移,caspase非依赖途径由此发挥重要作用。Objective To test the hypothesis that caspase-independent factor, apoptosis-inducing factor (AIF) was essential for the neuronal cell death pathway after postischemic hyperthermia by mediating apoptotic death in experimental ischemia related hyperthermia in rat. Methods Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and subsequently were maintained to hyperthermia. Animals in which group treated MCAO with normothermia and sham-operated controls as Animal behavioral scores, infarct volume and immunohistochemistry of AIF were observed at each of days 1, 2, 3 and 7 after operations. Double labeling and flow cytometry analysis were recorded with PC12 at different time points. Results Double labeling of PC12 culture and flow cytometry analysis demonstrated increased fluorescence intensity in the 30 min, 3 h respectively after hyperthermic group compared with normothermia and apoptosis ratio significantly different after hyperthermia. Meanwhile, TUNEL stainings revealed morphologic apoptotic changes at 3d. None of these effects was prevented by the wide-ranging caspase inhibitor. Conclusion Our data provided evidence for a caspase- independent pathway of programmed cell death that influences the course of postischemic hyperthermia.

关 键 词：脑卒中 高温 细胞凋亡 凋亡诱导因子 神经保护 

分 类 号：R743.3[医药卫生—神经病学与精神病学]