Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury
Caspase inhibition and limitation of myocardial infarct size: protection against lethal reperfusion injury
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DOI：
10.1038/sj.bjp.0703336
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发表时间：
2000-05-01
影响因子：
7.3
通讯作者：
Yellon, DM
中科院分区：
文献类型：
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作者：
Mocanu, MM;Baxter, GF;Yellon, DM
缺血再灌注损伤通过坏死和凋亡引起细胞死亡。半胱天冬酶激活是细胞凋亡中的主要事件。因此，我们研究了半胱天冬酶抑制剂在心肌梗死再灌注过程中的作用。大鼠离体心脏进行35分钟的冠状动脉闭塞和120分钟的再灌注。治疗组在再灌注早期灌注caspase抑制剂。我们评估了非选择性半胱天冬酶抑制剂（Z-VAD. foxin，0.1 μ M）、半胱天冬酶-8抑制剂（Z-IETD. foxin，0.07 μ M）、半胱天冬酶-9抑制剂（Z-LEHD. foxin，0.07 μ M）和半胱天冬酶-3抑制剂（Ac-DEVD.cmk，0.07 μ M）。所有半胱天冬酶抑制剂均限制了梗死面积（梗死风险比百分比：对照组38.5 +/- 2.6; Z-VAD. fk24.6 +/- 3.4; Z-LEHD. fk19.3 +/- 2.4; Z-IETD. fk23.0 +/- 5.4; Ac-DEVD.cmk 27.8 +/- 3.3;与对照组相比，单因素方差分析，P < 0.05）。我们的结论是，在早期再灌注抑制半胱天冬酶保护心肌免受致命的再灌注损伤。
Ischaemia-reperfusion injury causes cell death by both necrosis and apoptosis. Caspase activation is a major event in apoptosis. We therefore examined the effect of caspase inhibitors during reperfusion upon myocardial infarction. Rat isolated hearts were subjected to 35 min coronary occlusion and 120 min reperfusion. Treatment groups were perfused with caspase inhibitors during early reperfusion. We assessed a non-selective caspase inhibitor (Z-VAD.fmk, 0.1 mu M), a caspase-8 inhibitor (Z-IETD.fmk, 0.07 mu M), a caspase-9 inhibitor (Z-LEHD.fmk, 0.07 mu M) and a caspase-3 inhibitor (Ac-DEVD.cmk, 0.07 mu M). All caspase inhibitors limited infarct size (infarct-risk ratio per cent: control 38.5 +/- 2.6; Z-VAD.fmk 24.6 +/- 3.4; Z-LEHD.fmk 19.3 +/- 2.4; Z-IETD.fmk 23.0 +/- 5.4; Ac-DEVD.cmk 27.8 +/- 3.3; P < 0.05 when compared with control value, I-way ANOVA). We conclude that caspase inhibition during early reperfusion protects myocardium against lethal reperfusion injury.