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急性给予脂质体辅酶Q10可提高心肌组织水平,并改善对缺血再灌注损伤的耐受性。

Acute administration of liposomal coenzyme Q10 increases myocardial tissue levels and improves tolerance to ischemia reperfusion injury.

作者信息

Niibori K, Yokoyama H, Crestanello J A, Whitman G J

机构信息

Division of Cardiothoracic Surgery, Allegheny University/MCP, 3300 Henry Avenue, Philadelphia, Pennsylvania 19129, USA.

出版信息

J Surg Res. 1998 Oct;79(2):141-5. doi: 10.1006/jsre.1998.5411.

DOI:10.1006/jsre.1998.5411
PMID:9758729
Abstract

UNLABELLED

The antioxidant and bioenergetic effects of CoQ10 (CoQ) suggest it might be ideal therapy for acute myocardial ischemia. Its utility is limited by the requirement for enteral administration. This study related the administration of a new liposomal suspension of CoQ given intravenously to (1) serum and myocardial [CoQ] and (2) recovery of function, myocardial efficiency, and oxidant injury after cardiac ischemia and reperfusion (I/R). Rats (n = 8/group) were given liposomal CoQ 10 mg/kg iv or placebo (Control), 15 min (C-15), 30 min (C-30), and 60 min (C-60) before (1) measurement of serum and myocardial CoQ or (2) Langendorff perfusion of hearts subjected to 15 min equilibration, 25 min ischemia (37 degrees C), and 40 min reperfusion (RP). Developed pressure (DP) was measured via an intraventricular balloon and coronary flow was measured by a digital flow meter. Myocardial efficiency was defined as DP/MVO2 where MVO2 = microl O2 consumed/min/gram LV. At end RP hearts were assayed for CK, an oxidant sensitive enzyme. Maximum preischemic CoQ levels in serum and myocardium occurred 15 and 30 min after administration, respectively. At end reperfusion, C-30 hearts improved the most, recovering 75 +/- 4% of their preischemic DP while Control recovered only 52 +/- 6% (P < 0.03) as well as maintaining better myocardial efficiency (0.69 +/- 0.02 vs Control, 0.43 +/- 0.05) (P < 0.001). C-15, C-30, and C-60 groups all lost less CK activity after RP vs Control (P < 0.04).

CONCLUSION

(1) Serum and myocardial levels of CoQ can be raised acutely by iv liposomal CoQ. (2) Myocardial CoQ levels correlate best with I/R protection. (3) Acute iv CoQ improves function and efficiency and decreases oxidant injury after I/R. Intravenous CoQ may be effective clinically for acute cardiac ischemic syndromes.

摘要

未标记

辅酶Q10(CoQ)的抗氧化和生物能量作用表明它可能是急性心肌缺血的理想治疗方法。其应用因需要肠内给药而受到限制。本研究将静脉注射新的脂质体CoQ悬浮液与以下方面相关联:(1)血清和心肌中的[CoQ],以及(2)心脏缺血再灌注(I/R)后功能的恢复、心肌效率和氧化损伤。大鼠(每组n = 8)在以下情况前15分钟(C - 15)、30分钟(C - 30)和60分钟(C - 60)给予静脉注射10 mg/kg脂质体CoQ或安慰剂(对照组):(1)测量血清和心肌CoQ,或(2)对心脏进行Langendorff灌注,心脏先平衡15分钟,然后在37℃下缺血25分钟,再灌注40分钟(RP)。通过心室内球囊测量发展压力(DP),通过数字流量计测量冠状动脉血流量。心肌效率定义为DP/MVO2,其中MVO2 =每分钟每克左心室消耗的微升O2。在再灌注结束时,对心脏进行检测,测定氧化敏感酶肌酸激酶(CK)。血清和心肌中缺血前CoQ的最高水平分别在给药后15分钟和30分钟出现。在再灌注结束时,C - 30组心脏改善最为明显,恢复到缺血前DP的75±4%,而对照组仅恢复52±6%(P < 0.03),并且维持了更好的心肌效率(0.69±0.02对对照组0.43±0.05)(P < 0.001)。与对照组相比,C - 15、C - 30和C - 60组在再灌注后CK活性损失均较少(P < 0.04)。

结论

(1)静脉注射脂质体CoQ可使血清和心肌中的CoQ水平迅速升高。(2)心肌CoQ水平与I/R保护的相关性最佳。(3)急性静脉注射CoQ可改善I/R后的功能和效率,并减少氧化损伤。静脉注射CoQ在临床上可能对急性心脏缺血综合征有效。

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