二氮嗪对大鼠供心心肌线粒体结构及通透性的影响

目的:探讨线粒体ATP敏感性钾离子通道(mitoKATPC)开放剂二氮嗪(DE)对离体大鼠供心长时程低温保存时线粒体超微结构及线粒体渗透性转换孔(MPTP)开放的影响。方法:利用Langendorff离体鼠心灌注法,观察供心在4℃含不同浓度DE(15、30、45μmol/L)的Celsior保存液中保存9h后,复灌期心脏作功量(RPP)变化情况。比色法测定MPTP开放情况;透射电子显微镜观察心肌细胞线粒体超微结构的变化。结果:①Celsior保存液中加入30μmol/L的DE对促进长时程低温保存后供心收缩功能的恢复、减轻心肌细胞线粒体超微结构损伤和抑制MPTP开放的作用最显著。②DE的上述作用可分别被mitoKATP特异性阻断剂5-羟基葵酸盐(5-HD)及MPTP开放剂苍术苷(Atr)所取消。结论:DE可通过抑制MPTP开放而减轻由长时程低温保存导致的大鼠供心心肌线粒体超微结构的损伤。

Effects of diazoxide on the mitochondrial ultrastructure and permeability in donor rat myocardium

Objective：To investigate the effect of diazoxide（DE） on the myocardial ultrastructure and opening of mitochondrial permeabi-lity transition pore （MPTP） in donor rat heart suffered from long-term hypothermic preservation.Methods：The Langendorff model of isolated rat heart was used.The hearts were stored in 4 ℃ Celsior solution containing different concentration of DE （15,30,or 45 μmol/L） for 9 h followed by 60 min of reperfusion.The recovery of rate-pressure product（RPP） was observed.The opening of MPTP and myocardial mitochondria ultrastructure were also evaluated.Results：①As compared with the celsior solution preserved group,DE（30 μmol/L） increased recovery of RPP during reperfusion and inhibited the opening of MPTP.DE also alleviated the myocardial mitochondrial ultrastructure damage induced by long-term hypothermic preservation.②The above effects of DE were attenuated by a mitoKATP channel inhibitor 5-hydroxydecanoate and a MPTP opener atractyloside.Conclusion：In the donor rat heart,DE protects myocardial mitochondria ultrastructure against long-term hypothermic preservation injury via inhibiting the opening of MPTP.