Zimmer G, Evers J
Gustav-Embden-Zentrum der Biologischen Chemie, Universität Frankfurt am Main, F.R.G.
Basic Res Cardiol. 1988 Jul-Aug;83(4):445-51. doi: 10.1007/BF02005830.
The cardioprotective concentration range of the thiol drug 2-mercaptopropionylglycine (MPG) was investigated during reoxygenation after 30 min of hypoxia. It was found that aortic flow and frequency were increased by 1 mM MPG. Coronary flow, systolic and diastolic pressure were not significantly influenced by the drug. Mitochondria, isolated from hearts after termination of the perfusion phases, revealed increased values of RCI, when MPG had been present in the previous reoxygenation phase at 1 mM concentration. 5 mM MPG no longer showed a protective influence on the above cardiac and mitochondrial parameters. ATPase activities were decreased at 1 mM MPG by 14% and at 5 mM MPG by 40% of the controls. The latter concentration of MPG also doubled the inhibitory action of carboxyatractyloside on ATPase activity, indicating a structural change of the adenine nucleotide carrier. 1 mM MPG is considered an optimal therapeutic range in this model. The mechanism of action most probably includes an SH/-S-S-interchange reaction as well as a free radical scavenging mechanism. For many thiols, the latter is known to occur in the presence of metal ions.
在缺氧30分钟后的复氧过程中，研究了硫醇类药物2-巯基丙酰甘氨酸（MPG）的心脏保护浓度范围。发现1 mM MPG可使主动脉流量和频率增加。冠状动脉流量、收缩压和舒张压不受该药物的显著影响。在灌注阶段结束后从心脏分离出的线粒体显示，当MPG在先前的复氧阶段以1 mM浓度存在时，RCI值增加。5 mM MPG对上述心脏和线粒体参数不再显示出保护作用。1 mM MPG时ATP酶活性比对照组降低了14%，5 mM MPG时降低了40%。后一浓度的MPG还使羧基苍术苷对ATP酶活性的抑制作用增加了一倍，表明腺嘌呤核苷酸载体发生了结构变化。在该模型中，1 mM MPG被认为是最佳治疗范围。其作用机制很可能包括SH/-S-S-交换反应以及自由基清除机制。对于许多硫醇类物质，已知后者在金属离子存在的情况下会发生。
