Bax deficiency reduces infarct size and improves long-term function after myocardial infarction
Bax deficiency reduces infarct size and improves long-term function after myocardial infarction
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DOI：
10.1385/cbb:47:1:11
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Birk, E.
中科院分区：
文献类型：
--
作者：
Hochhauser, E.;Cheporko, Y.;Birk, E.
我们以前发现，心肌缺血/再灌注损伤后，离体心脏从bax基因敲除小鼠[Bax（-/-）]表现出更高的心脏保护比野生型。我们在此探讨Bax（-/-）在体内心肌梗死（MI）后的作用。研究了纯合子Bax（-/-）和匹配的野生型。对小鼠进行左冠状动脉前降支（LAD）的手术结扎。心肌梗死后28 d，Bax（-/-）组左室舒张末内径、收缩末内径的进行性增加明显小于Bax（+/+）组（p < 0.03）。同时，在MI后28天，与野生型相比，Bax（-/-）的缩短分数更高（35 +/- 4.1%和27 +/-2.5%，p < 0.001），梗死面积更小（24 +/-3.7%和37 +/-3.3%，p < 0.001）。心肌梗死后24 h，Bax（-/-）组血清肌酸激酶和乳酸脱氢酶的释放低于Bax（+/+）组。Caspase 3活性在MI后2小时仅在野生型中升高，但在MI后I和28天降低至基线值。Bax基因敲除小鼠心脏表现出减少梗死面积和改善心肌功能后，永久性冠状动脉闭塞。Bax基因似乎在心肌梗死后反应中起重要作用，应进一步研究。
We have previously found that, following myocardial ischemia/reperfusion injury, isolated hearts from bax gene knockout mice [Bax(-/-)] exhibited higher cardioprotection than the wild-type. We here explore the effect of Bax(-/-), following myocardial infarction (MI) in vivo. Homozygotic Bax(-/-) and matched wild-type were studied. Mice underwent surgical ligation of the left anterior descending coronary artery (LAD). The progressive increase in left-ventricular end diastolic diameter, end systolic diameter, in Bax(-/-) was significantly smaller than in Bax(+/+) at 28 d following MI (p < 0.03) as seen by echocardiography. Concomitantly, fractional shortening was higher (35 +/- 4.1% and 27 +/- 2.5%, p < 0.001) and infarct size was smaller in Bax(-/-) compared to the wild-type at 28 days following MI (24 +/- 3.7 % and 37 +/- 3.3%, p < 0.001). Creatine kinase and lactate dehydrogenase release in serum were lower in Bax(-/-) than in Bax(+/+) 24 h following MI. Caspase 3 activity was elevated at 2 h after MI only in the wild-type, but reduced to baseline values at I and 28 d post-MI. Bax knockout mice hearts demonstrated reduced infarct size and improved myocardial function following permanent coronary artery occlusion. The Bax gene appears to play a significant role in the post-MI response that should be further investigated.