全脑缺血再灌注后Fas、TNFR1蛋白的表达与细胞凋亡的关系及Bcl-2过度表达对其的影响  

Fas and TNFR1 expressions after cerebral ischemia and reperfusion in rats:association with cell apoptosis and the effects of Bcl-2 overexpression

作　　者：吴刚[1] 薛荣亮[1] 吕建瑞[1] 李伟[1] 雷晓鸣[1] 

机构地区：[1]西安交通大学医学院第二附属医院麻醉科,陕西西安710004

出　　处：《南方医科大学学报》2011年第8期1298-1303,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(30070731);陕西省科技攻关课题(2009K16-02)~~

摘　　要：目的通过观察全脑缺血再灌注后大鼠海马回Fas、TNFR1蛋白的表达与细胞凋亡及Bcl-2过度表达时对其表达的影响,探讨全脑缺血再灌注后Bcl-2过度表达对Fas、TNFR1介导凋亡的影响及可能机制。方法健康雄性SD大鼠90只,随机分成3组:假手术组(PO组)、缺血再灌注组(IR组)和Bcl-2过度表达组(BT组)。采用4-VO法建立SD大鼠全脑缺血再灌注模型,应用HE染色、免疫组化和TUNEL方法检测Bcl-2、Fas和TNFR1在CA1及CA3区的表达及细胞凋亡。结果 HE染色显示:IR组CA1区缺血48 h后神经元数目减少,排列紊乱,间质水肿;CA3区少数细胞结构不清。BT组变化不明显。免疫组化染色显示:Fas在IR组中CA1区6 h达高峰,BT组强度弱于IR组(P<0.05)。TNFR1在IR组CA1区24 h达到高峰,BT组强度弱于IR组(P<0.05)。两者PO组CA1、CA3区表达为阴性。细胞凋亡检测:IR组在缺血再灌注后6h,CA1、CA3区凋亡细胞开始增加,24～48 h为高峰。BT组弱于IR组(P<0.05)。结论 Fas和TNFR1蛋白在全脑缺血再灌注后海马CA1区及CA3区都有表达,只是表达强弱及细胞分布不同,提示死亡受体参与了全脑缺血再灌注损伤。Bcl-2过度表达能减弱Fas和TNFR1蛋白在全脑缺血再灌注后的表达,明显减少凋亡细胞数,提示Bcl-2过度表达对全脑缺血再灌注损伤有保护作用。Objective To investigate the effect of Bcl-2 overexpression on Fas and TNFR1-mediated apoptosis and its possible mechanism in rat hippocampus following global ischemia/reperfusion（IR）.Methods Ninety healthy male SD rats were randomly divided into sham operated group,IR group and Bcl-2 overexpression group（BT group）.Rat model of global IR was established by the 4-V0 method.The expressions of Bcl-2,Fas and TNFR1 and the cell apoptosis in the CA1 and CA3 regions were examined by HE staining,immunohistochemistry and TUNEL method.Results In IR group,the neurons in the CA1 region showed an obvious reduction in number with disordered arrangement and interstitial edema 48 h after global IR.Such changes were not obvious in BT group.Immunohistochemistry showed that Fas expression in the CA1 region reached the peak level at 6 h in IR group with a greater expression intensity than that in BT group（P0.05）.TNFR1 was expressed at a higher level in IR group than in BT group（P0.05）,reaching the peak level at 24 h.In the sham group,the expression of Fas and TNFR1 was not detected the in CA1 and CA3 regions.Global IR caused increased cell apoptosis in the CA1 and CA3 regions,starting at 6 h and reached peak at 24 to 48 h.The cell apoptosis was less obvious in BT group（P0.05）.Conclusion Fas and TNFR1 are expressed in the CA1 and CA3 regions after global IR in rats,suggesting the involvement of death receptor in cerebral IR injury.Bcl-2 overexpression decreases the expression of Fas and TNFR1 and cell apoptosis after global IR,thus offering protective effect against cerebral IR injury.

关 键 词：缺血再灌注损伤 FAS TNFR1 BCL-2 细胞凋亡 

分 类 号：R743[医药卫生—神经病学与精神病学]