Bax ablation protects against myocardial ischemia-reperfusion injury in transgenic mice
Bax ablation protects against myocardial ischemia-reperfusion injury in transgenic mice
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DOI：
10.1152/ajpheart.00783.2002
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发表时间：
2003-06-01
影响因子：
4.8
通讯作者：
Vidne, BA
中科院分区：
文献类型：
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作者：
Hochhauser, E;Kivity, S;Vidne, BA
本研究在三组小鼠中研究了细胞凋亡原Bax基因在缺血再灌注损伤中的作用：缺失Bax基因的纯合子敲除小鼠(Bax(-/-))、杂合子小鼠(Bax(+/-))和野生型小鼠(Bax(+/+))。离体心脏先缺血30分钟，37℃，然后再灌流120分钟。Bax缺陷组和Bax(+/+)组在稳定状态和再灌流120min时的左心室发展力分别为1,411+/-177和1,161+/-137 mg和485+/-69和306+/-68 mg。Bax(-/-)心脏I/R后心功能改善伴随着肌酸激酶释放、caspase3活性、不可逆性缺血性损伤和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性心肌细胞数量的减少。电子显微镜评估显示，Bax缺陷小鼠的线粒体和核染色质结构的损伤有所减轻。在BAX(+/-)心脏中，损伤标记为中等。BAX基因敲除的心脏对I/R损伤的超强耐受性使该基因成为治疗严重和顽固性心肌缺血患者的潜在靶点。
The role of the proapototic Bax gene in ischemia-reperfusion (I/R) injury was studied in three groups of mice: homozygotic knockout mice lacking the Bax gene (Bax(-/-)), heterozygotic mice (Bax(+/-)), and wild-type mice (Bax(+/+)). Isolated hearts were subjected to ischemia (30 min, 37degreesC) and then to 120 min of reperfusion. The left ventricular developed force of Bax-deficient vs. Bax(+/+) hearts at stabilization and at 120 min of reperfusion was 1,411 +/- 177 vs. 1,161 +/- 137 mg and 485 +/- 69 vs. 306 +/- 68 mg, respectively. Superior cardiac function of Bax(-/-) hearts after I/R was accompanied by a decrease in creatine kinase release, caspase 3 activity, irreversible ischemic injury, and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cardiomyocytes. Electron microscopic evaluation revealed reduced damage to mitochondria and the nuclear chromatin structure in Bax-deficient mice. In the Bax(+/-) hearts, the damage markers were moderate. The superior tolerance of Bax knockout hearts to I/R injury recommends this gene as a potential target for therapeutic intervention in patients with severe and intractable myocardial ischemia.