cas pase抑制剂对大鼠缺血再灌注脑组织细胞凋亡和Aβ的影响  

Effects of Inhibitor of Caspase-3 to Apoptosis and β-amyloid Protein in Focal Cerebral Ischemia-reperfusion of Rat Brain

作　　者：樊丽超[1] 于永发[1] 张莹[1] 

机构地区：[1]哈尔滨医科大学附属第二医院神经科,黑龙江哈尔滨150086

出　　处：《中国神经免疫学和神经病学杂志》2005年第6期327-330,共4页Chinese Journal of Neuroimmunology and Neurology

摘　　要：目的研究大鼠局灶性脑缺血再灌注损伤时caspase-3抑制剂对细胞凋亡及β-淀粉样蛋白(Aβ)表达的影响。方法采用线栓法制作大鼠局灶性脑缺血再灌注模型,将Wistar大鼠分为假手术组、缺血再灌注组、Ac-DEVD-CHO组和二甲亚砜(DMSO)组。大脑中动脉阻塞2 h再灌注48 h,Ac-DEVD-CHO组于大脑中动脉阻塞后30 min向小脑延髓池注入caspase-3抑制剂Ac-DEVD-CHO。采用TUNEL染色检测细胞凋亡,免疫组化SABC法检测Aβ的表达。结果与缺血再灌注组比较,Ac-DEVD-CHO组凋亡细胞百分率显著降低(P<0.05),Aβ表达显著减少(P<0.05)。结论caspase-3抑制剂可减少脑缺血再灌注损伤时细胞凋亡的发生及Aβ表达,提示局灶性脑缺血再灌注损伤时可能存在caspase-3对Aβ前体蛋白APP的降解,使Aβ产生增多并促进凋亡的发生。Objective To investigate the effects of inhibitor of caspasc-3 on apoptosis and the expression of β-amyloid protein in focal cerebral isehemia-repcrfusion injury of rat brain. Methods Nylon thread embolism-technique was select to set up animal model of the middle cerebral artery occlusion. Wistar rats were divided into for 4 groups： sham operation, ischemia-rcpcrfusion, Ac-DEVD-CHO and DMSO group. After 2 hours of ischemia, the time of rcpcrfusion was 48 hours. Ac-DEVD-CHO （iv, 4μL） was injected slowly into ccrebellomedullary cistern after 30 min of the treated group. DMSO was injected into ccrcbcllomcdullary cistern of the DMSO group. Apoptosis was detected by terminal dcoxynucleotidyl-trallsfcrase mediated dUTP nick end labeling （TUNEL）. β-amyloid protein expression was detected by immunohistochemistry method. Results In the treated group with Ac-DEVD-CHO, the apoptotic ceils were significantly decreased （P〈0. 05）and the expression of β-amyloid pro- tein was prominently decreased （P〈0.05）than ischcmia-rcpcrfusion group. Conclusions Inhibitor of caspase-3 decreased apoptosis as well as the expression of β-amyloid protein on focal cerebral ischemia-reperfusion of rat brain. It indicats that caspase-3 probably decompose β-amyloid precursor protein and increaseβ-amyloid protein, to induce apoptosis in ischemia-reperfusion injury.

关 键 词：CASPASE-3抑制剂 Β-淀粉样蛋白 脑缺血再灌注损伤 凋亡 

分 类 号：R743[医药卫生—神经病学与精神病学]