大蒜素通过调节Bcl-2,Bax及NF-κB表达而抑制大鼠缺血/再灌注心肌细胞凋亡(英文)  

Allitridum attenuates ischemia/reperfusion-induced apoptotic cell death by modulating expression of Bcl-2,Bax and NF-κB

作　　者：史春志[1] 张绘莉[1] 吴士尧[1] 严毓勤[1] 冯义柏[2] 

机构地区：[1]上海交通大学医学院附属第九人民医院心脏科,上海200011 [2]华中科技大学附属协和医院心脏科,湖北武汉430030

出　　处：《心脏杂志》2010年第6期814-820,共7页Chinese Heart Journal

基　　金：supported in part by the Laboratory of Pathology,Immunology and Molecular Biology and Animal Center of Tongji Medical college of Huazhong University of Science and Technology

摘　　要：目的:探讨大蒜素预处理对在体大鼠心肌缺血/再灌注(I/R)损伤的保护作用、对心肌细胞凋亡的影响及Bcl-2,Bax,NF-κB是否参与抗凋亡作用。方法:建立大鼠在体心肌I/R损伤模型,将48只大鼠随机分为正常对照(Con)组、I/R组和大蒜素预处理(AP)组;各组均测定心肌梗死范围[IS/AAR(%),TTC法]、再灌注后血清肌酸磷酸肌酶同工酶MB(CK-MB)和超氧化物歧化酶(SOD)活性,并应用DNA琼脂糖凝胶电泳及TUNEL法检测各组凋亡指数(AI)、Bcl-2,Bax表达及NF-κB核结合活性。结果:AP组较I/R组IS/AAR(%)[(21.8±1.5)%vs.(44.6±4.6)%,P<0.01],CK-MB[(16.4±1.6)vs.(34.1±1.8)U/L,P<0.01]明显降低,SOD[(2 337±215)vs.(1 219±187)U/mg pro,P<0.01]明显增高。AP组AI较I/R组明显降低[(7.0±1.2)%vs.(4.0±3.0)%,P<0.01]。Bcl-2表达明显增加,Bax表达明显减少,NF-κB核结合活性明显降低。结论:大蒜素有明显抗大鼠心肌I/R损伤作用能与抗心肌细胞凋亡有关,对Bcl-2,Bax及NF-κB表达的调控起重要作用。AIM： To investigate the roles of Bcl-2, Bax and NF-κB in the anti-apoptosis effect of allitridum. METHODS： Sodium pentobarbital-anesthetized Sprague Dawley （SD） rats underwent 30 min of left anterior descending （LAD） coronary occlusion followed by 120 min of reperfusion. Forty-eight rats were randomly divided into three groups： control （CON, n = 12 ）, ischemia/reperfusion （I/R, n = 18） group and allitridum pretreatment （AP, n = 18） group. Twenty-four h before oper- ation, allitridum was given to the AP group and saline was administered to the other groups. CON group underwent only sham operation, whereas the other two groups underwent I/R operation. Infarct size [ IS/AAR （ % ） ] was measured in the I/R group and AP group, and creatine kinase isoenzyme-MB （CK-MB）, superoxide dismutase （SOD） and apoptosis index （AI） by TUNEL staining were measured in each group. DNA fragmentation agarose gel electrophoresis was conducted on isolated DNA and the expression of Bcl-2 and Bax protein and the activity of NF-κB were measured, respectively, by immunohisto- chemistry and electrophoretic mobility assay （EMSA） in each group. RESULTS： Allitridum pretreatment decreased the infarct size compared with that in I/R group [ （ 21.8 ＋ 1.5 ） % vs. （44. 6 ＋- 4. 6 ） %, P 〈 0. 01 ], CK-MB [ （ 16. 4 ＋ 1.6） U/L vs. （34. 1 ＋ 1.8） U/L, P 〈0. 01 ]. However, SOD levels in AP group were higher than those in I/R group [ （2 337 ＋ 215） U/mg pro vs. （ 1 219 ＋ 187） U/rag pro, P 〈0. 01 ]. AI in I/R group was higher than in AP group [ （4. 0 ＋3.0）% vs. （7. 0 ＋ 1.2）%, P 〈0. O1 ], which was consistent with the result of DNA fragmentation agarose gel electrophoresis. No immunoreactivity of Bcl-2 was observed in CON group. Bcl-2 immunoreactivity was weakly expressed in the I/R group and strongly expressed in the peri-necrosis zone in the AP group. The expression of Bax significantly increased in I/R group but was weaker in the AP group. NF-κB binding

关 键 词：缺血/再灌注 大蒜素 心肌 凋亡 Bcl-2 BAX NF-ΚB 

分 类 号：R542.2[医药卫生—心血管疾病]