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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

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第6期
页码:
814-820
栏目:
基础研究
出版日期:
2010-08-23

文章信息/Info

Title:
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
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
Author(s):
SHI Chun-zhi1;  ZHANG Hui-li1;  WU Shi-yao1;  YAN Yu-qin1;  FENG Yi-bai2
1.Department of Cardiology, Ninth Hospital Affiliated to Medical College, Shanghai Jiaotong University, Shanghai 200011, China; 2.Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
关键词:
缺血/再灌注; 大蒜素; 心肌; 凋亡; Bcl-2; Bax; NF-κB
Keywords:
myocardium;  allitridum;  ischemia/reperfusion;  apoptosis;  Bcl-2;  Bax;  NF-κB
分类号:
R542.2
DOI:
-
文献标识码:
A
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。
Abstract:
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 operation, 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 immunohistochemistry 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/mg 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<0.01］, 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 activity was present at low levels in CON group but significantly increased in the I/R group. Allitridum markedly inhibited NF-κB binding in the I/R group. CONCLUSION: Allitridum has an obvious effect of protecting myocardium against I/R injury and decreasing infarcted zone. The protective effect is probably achieved through decreasing myocardium apoptosis in I/R injury and modulating the expression of Bcl-2 and Bax and the binding activity of NF-κB.

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备注/Memo

备注/Memo:
收稿日期：2009-08-21.作者简介: 史春志，博士Email:chunzhis@163.com
更新日期/Last Update: 2010-08-22