Niibori K, Wroblewski K P, Yokoyama H, Crestanello J A, Whitman G J
Department of Cardiothoracic Surgery, Allegheny University/MCP, Philadelphia, PA 19129, USA.
Biofactors. 1999;9(2-4):307-13. doi: 10.1002/biof.5520090228.
The antioxidant and bioenergetic effects of CoQ10 are well known but its clinical utility is limited by the requirement for enteral administration. A newly developed liposomal CoQ10 (CoQ) is water soluble and capable of intravenous administration. The purpose of this study is to determine the mechanism by which acute administration CoQ protects myocardium from reperfusion (Rp) injury. Rats were pretreated with CoQ 10 mg/kg i.v. 30 min prior to the experiment. Control rats were pretreated with liposome only. Hearts were excised and subjected to equilibration, 25 min of normothermic ischemia and 40 min of Rp on a Langendorff apparatus. At end Rp, CoQ hearts recovered 74 +/- 5% of their DP vs. 50 +/- 9% in control (p < 0.05). Aerobic efficiency was maintained (0.66 +/- 0.02 vs. control, 0.5 +/- 0.04, p < 0.003) and CoQ hearts lost less CK activity vs. control (p < 0.02). PCr and ATP were higher than control (p < 0.05, 0.02, respectively). Results show that i.v. CoQ improves recovery of function, aerobic efficiency, CK activity, and recovery of PCr and ATP after Rp. This suggests that acute administration of liposomal CoQ improves myocardial tolerance to I/R via its role as an antioxidant as well as improving oxygen utilization and high energy phosphate production.
辅酶Q10的抗氧化和生物能量作用已广为人知,但其临床应用因需要肠内给药而受到限制。新开发的脂质体辅酶Q10(CoQ)是水溶性的,能够静脉给药。本研究的目的是确定急性给予CoQ保护心肌免受再灌注(Rp)损伤的机制。在实验前30分钟,给大鼠静脉注射10mg/kg CoQ进行预处理。对照大鼠仅用脂质体预处理。取出心脏,在Langendorff装置上进行平衡、25分钟的常温缺血和40分钟的Rp。在Rp结束时,CoQ处理的心脏恢复了其舒张期压力的74±5%,而对照组为50±9%(p<0.05)。有氧效率得以维持(分别为0.66±0.02对对照组0.5±0.04,p<0.003),且CoQ处理的心脏与对照组相比,肌酸激酶活性损失更少(p<0.02)。磷酸肌酸(PCr)和三磷酸腺苷(ATP)高于对照组(分别为p<0.05,0.02)。结果表明,静脉注射CoQ可改善Rp后心脏功能的恢复、有氧效率、CK活性以及PCr和ATP的恢复。这表明急性给予脂质体CoQ通过其作为抗氧化剂的作用以及改善氧利用和高能磷酸盐生成,提高了心肌对缺血/再灌注的耐受性。