Abadie C, Ben Baouali A, Maupoil V, Rochette L
Laboratoire de Physiopathologie et Pharmacologie Cardiovasculaires Expérimentales, Facultés de Médecine et de Pharmacie, Dijon, France.
Free Radic Biol Med. 1993 Aug;15(2):209-15. doi: 10.1016/0891-5849(93)90061-x.
Recently, it has been reported that alpha-tocopherol analogues reduce infarct size in vivo in the rat and improve contractility upon reperfusion following global ischemia in isolated rat hearts. In the present study, we have thus investigated the effects of the hydrophilic alpha-tocopherol analogue MDL 74366 on nonenzymatic lipid peroxidation using a tissue homogenate method and reperfusion-induced arrhythmias following a local ischemia in isolated working rat hearts. Lipoperoxide (LPO) production was inhibited in a concentration-dependent manner in spontaneous as well as in induced peroxidations. The concentration resulting in a 50% inhibition (IC50) was around 2 microM. MDL 74366 treatment had no significant effect on baseline heart rate and cardiac output values. However, MDL 74366 decreased the incidence of reperfusion arrhythmias (ventricular tachycardia, VT; ventricular fibrillation, VF). The coincidence observed between the protective effect of MDL 74366 against tissue LPO formation and the preventive effect of this alpha-tocopherol analogue in the heart during the ischemia-reperfusion sequence confirms that vitamin E has beneficial effects against induced oxidative damage.
最近，有报道称α-生育酚类似物可减小大鼠体内的梗死面积，并改善离体大鼠心脏在全心缺血后再灌注时的收缩能力。在本研究中，我们因此使用组织匀浆法研究了亲水性α-生育酚类似物MDL 74366对非酶性脂质过氧化的影响，以及对离体工作大鼠心脏局部缺血后再灌注诱导的心律失常的影响。在自发性以及诱导性过氧化反应中，脂质过氧化物（LPO）的产生均以浓度依赖性方式受到抑制。产生50%抑制作用（IC50）的浓度约为2微摩尔。MDL 74366处理对基础心率和心输出量值无显著影响。然而，MDL 74366降低了再灌注心律失常（室性心动过速，VT；心室颤动，VF）的发生率。MDL 74366对组织LPO形成的保护作用与该α-生育酚类似物在心脏缺血-再灌注过程中的预防作用之间的一致性证实，维生素E对诱导的氧化损伤具有有益作用。
