Packer L, Valenza M, Serbinova E, Starke-Reed P, Frost K, Kagan V
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Arch Biochem Biophys. 1991 Aug 1;288(2):533-7. doi: 10.1016/0003-9861(91)90231-7.
L-Propionyl-carnitine is known to improve the recovery of myocardial function and metabolic parameters reduced in the course of ischemia-reperfusion of the heart. The mechanism of this protective effect of L-propionyl-carnitine is not fully understood. The purpose of this study was to elucidate the effects of L-propionyl-carnitine in Langendorff perfused rat hearts subjected to 40 min of ischemia followed by 20 min of reperfusion. We tested the hypothesis that L-propionyl-carnitine suppresses generation of oxygen radicals and subsequent oxidative modification of myocardial proteins during reperfusion. Our data show that the protective effect of L-propionyl-carnitine in the course of ischemia-reperfusion is highly significant in terms both of mechanical properties of the heart (developed pressure) and of high-energy phosphates (ATP, creatine phosphate). Myocardial creatine phosphokinase (CPK) activity decreased in the course of the reperfusion period. The loss of CPK activity was partially prevented by L-propionyl-carnitine. Two other effects were observed when L-propionyl-carnitine was present in the perfusion solution: (i) the reperfusion-induced sharp increase in oxidative protein modification was completely prevented as detected by the formation of protein carbonyls, and (ii) generation of hydroxyl radicals was significantly inhibited as detected by the formation of the adducts with the spin trap 5,5-dimethyl-1-pyrroline-1-oxide. We conclude that the protective effect of L-propionyl-carnitine against ischemia-reperfusion injury of the heart is at least due in part to its ability to suppress the development of oxidative stress and free radical damage.
已知L-丙酰肉碱可改善心脏缺血再灌注过程中降低的心肌功能和代谢参数的恢复。L-丙酰肉碱这种保护作用的机制尚未完全了解。本研究的目的是阐明L-丙酰肉碱对离体灌流的大鼠心脏（经40分钟缺血后再灌注20分钟）的影响。我们检验了这样一个假设，即L-丙酰肉碱在再灌注期间可抑制氧自由基的产生以及随后心肌蛋白的氧化修饰。我们的数据表明，L-丙酰肉碱在缺血再灌注过程中的保护作用在心脏机械性能（舒张末压）和高能磷酸盐（三磷酸腺苷、磷酸肌酸）方面均非常显著。在再灌注期间，心肌磷酸肌酸激酶（CPK）活性降低。L-丙酰肉碱可部分防止CPK活性的丧失。当灌注液中存在L-丙酰肉碱时，还观察到另外两种效应：（i）通过蛋白质羰基的形成检测发现，再灌注诱导的氧化蛋白修饰急剧增加被完全阻止；（ii）通过与自旋捕获剂5,5-二甲基-1-吡咯啉-N-氧化物形成加合物检测发现，羟自由基的产生受到显著抑制。我们得出结论，L-丙酰肉碱对心脏缺血再灌注损伤的保护作用至少部分归因于其抑制氧化应激和自由基损伤发展的能力。
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