异戊巴比妥保护缺血心肌细胞

The Reversible Inhibitor of Complex Ⅰ Amobarbital Protects the Ischemic Heart

目的探究异戊巴比妥(amobarbital)心肌保护作用的内在分子机制。方法把体外再灌注鼠心分为3组:平衡组(CON组,平衡90min),缺血组(ISC组,平衡15min,缺血25min,再灌注50min),药物组[AMO组,以3种不同浓度(1.25、2.50、3.75mmol/L)的异戊巴比妥于缺血之前给药,余与ISC组相同]。测量心脏功能,活性氧族(reactive oxygen species,ROS)生成量,心磷脂含量,线粒体复合体Ⅰ活性以及线粒体膜通道孔(mitochondrial permeability transition pore,mPTP)的开放等指标。结果异戊巴比妥使心脏功能明显改善。与CON组相比,其它2组线粒体复合体Ⅰ活性分别降低44%(ISC组)和20%(AMO组),ROS生成增加86%(ISC组)和18%(AMO组),心磷脂含量降低34%(ISC组)和11%(AMO组)。而且异戊巴比妥可以抑制环孢素A敏感的线粒体膜通道孔的开放。结论异戊巴比妥对缺血再灌注心肌有保护作用。

Objective In order to elucidate the molecular mechanism underlying the cardioprotection afforded by amobarbital（AMO）, the effect of AMO treatment on cardiac function, ROS production, cardiolipin content, complex I activity and mPTP was investigated in rat hearts under ischemia and reperfusion conditions. Methods Isolated perfused rat hearts were divided into three groups： control group （CON group, equilibrating 90 min）, ischemia group （ISC group, equilibrating 15 rain and subjected to 25 rain of ischemia and 50 min of reperfusion）, drug groups （AMO groups, three concentrations of AMO were given just before ischemia, and the rest same as ISC）. Results Cardiac function was obviously improved. Compared with the controls, complex I activity was reduced by 44% and 20% in mitochondria isolated from isehemic and AMO heart, respectively; ROS production was increased by 86 % and 18 % respectively; The content of cardiolipin was reduced by 34 % and by 11 respectively. Furthermore, this experiment demonstrated that AMO inhibited CsA-sensitive, low-conductance transient mPTP opening. Conclusion These results may provide an explanation for some factors responsible for AMO cardioprotective effects during ischemia and reperfusion.