Ferrara N, Abete P, Ambrosio G, Landino P, Caccese P, Cirillo P, Oradei A, Littarru G P, Chiariello M, Rengo F
Istituto di Medicina Interna, Università degli Studi di Napoli, Federico II, Italy.
J Pharmacol Exp Ther. 1995 Aug;274(2):858-65.
Previous studies have shown that acute exogenous administration of coenzyme ubiquinone (CoQ10) can protect the heart against oxidant-mediated injury. The aim of this study was to investigate whether protection against cardiac oxidative stress could be obtained by increasing tissue levels of CoQ10, as achieved by chronic CoQ10 supplementation. Wistar rats were randomly divided into two groups: a control group given standard diet and a test group receiving diet supplemented with CoQ10 (5 mg/kg/day) for 4 weeks. Functional and metabolic changes induced by oxidative stress were investigated in isolated perfused hearts and in papillary muscles. Tissue concentrations of ubiquinones were significantly higher in the left ventricle of treated rats than in controls. H2O2 infusion (60 microM for 60 min) induced marked alterations of both developed pressure, which decreased to -58.8 +/- 16.8% of base line and end-diastolic pressure which increased almost 13-fold. These effects were reduced significantly (P < .05) in hearts from CoQ10-supplemented rats (-13.8 +/- 2.3 and +375.0 +/- 42.5%, respectively). In the same hearts, cumulative release of oxidized glutathione (a specific marker of oxidative stress) was 450.2 +/- 69.2 nmol/g of wet weight in the control group and only 89.6 +/- 22.3 nmol/g of wet weight in treated hearts (P < .01). In papillary muscles, after 60 min of perfusion with H2O2, active tension decreased, largely in controls whereas it was almost unchanged in the treated group (-34.4 +/- 7.5% of baseline vs. -0.1 +/- 0.05%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明,急性外源性给予辅酶Q10(CoQ10)可保护心脏免受氧化介导的损伤。本研究的目的是调查通过长期补充CoQ10提高组织中CoQ10水平是否能实现对心脏氧化应激的保护作用。将Wistar大鼠随机分为两组:一组给予标准饮食作为对照组,另一组给予补充CoQ10(5毫克/千克/天)的饮食,持续4周作为试验组。在离体灌注心脏和乳头肌中研究氧化应激诱导的功能和代谢变化。治疗组大鼠左心室中泛醌的组织浓度显著高于对照组。注入过氧化氢(60微摩尔,持续60分钟)可引起显著变化,包括心脏发育压力降至基线的-58.8±16.8%,舒张末期压力几乎增加13倍。在补充CoQ10的大鼠心脏中,这些影响显著减轻(P<0.05)(分别为-13.8±2.3%和+375.0±42.5%)。在同样的心脏中,氧化型谷胱甘肽(氧化应激的特异性标志物)的累积释放量在对照组为450.2±69.2纳摩尔/克湿重,而在治疗组心脏中仅为89.6±22.3纳摩尔/克湿重(P<0.01)。在乳头肌中,用过氧化氢灌注60分钟后,主动张力下降,在对照组中下降幅度很大,而在治疗组中几乎没有变化(相对于基线分别为-34.4±7.5%和-0.1±0.05%,P<0.05)。(摘要截断于250字)