Mocanu M M, Baxter G F, Yellon D M
The Hatter Institute, Division of Cardiology, University College Hospitals & Medical School, Grafton Way, London, WC1E 6DE.
Br J Pharmacol. 2000 May;130(2):197-200. doi: 10.1038/sj.bjp.0703336.
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 microM), a caspase-8 inhibitor (Z-IETD.fmk, 0.07 microM), a caspase-9 inhibitor (Z-LEHD.fmk, 0.07 microM) and a caspase-3 inhibitor (Ac-DEVD.cmk, 0.07 microM). 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, 1-way ANOVA). We conclude that caspase inhibition during early reperfusion protects myocardium against lethal reperfusion injury.
缺血再灌注损伤通过坏死和凋亡两种方式导致细胞死亡。半胱天冬酶激活是凋亡过程中的一个主要事件。因此,我们研究了再灌注期间半胱天冬酶抑制剂对心肌梗死的影响。将大鼠离体心脏进行35分钟的冠状动脉阻塞和120分钟的再灌注。治疗组在早期再灌注期间用半胱天冬酶抑制剂进行灌注。我们评估了一种非选择性半胱天冬酶抑制剂(Z-VAD.fmk,0.1微摩尔)、一种半胱天冬酶-8抑制剂(Z-IETD.fmk,0.07微摩尔)、一种半胱天冬酶-9抑制剂(Z-LEHD.fmk,0.07微摩尔)和一种半胱天冬酶-3抑制剂(Ac-DEVD.cmk,0.07微摩尔)。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.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;与对照值相比,P<0.05,单因素方差分析)。我们得出结论,早期再灌注期间抑制半胱天冬酶可保护心肌免受致命的再灌注损伤。