Patrignani Paola, Tacconelli Stefania
Department of Medicine and Center of Excellence on Aging, G. d'Annunzio University, Chieti, Italy.
Biomarkers. 2005 Nov;10 Suppl 1:S24-9. doi: 10.1080/13547500500215084.
Several lines of evidence suggest that reactive oxygen species play a role in the development of vasculopathies, including those that define atherosclerosis, hypertension and restenosis after angioplasty. Confused picture emerging from prospective clinical trials of anti-oxidants may reflect inadequacy of traditional indices of lipid peroxidation in the recruitment of appropriate patients and in guiding the selection of the appropriate dose of anti-oxidant to be tested. Ex vivo indices of oxidant stress could have questionable veracity in assessing the actual rate of lipid peroxidation in vivo. The measurement of F(2)-isoprostanes (F(2)-iPs), formed non-enzimatically through free radical catalysed attack on esterified arachidonate, provides a reliable tool for identifying populations with enhanced rates of lipid peroxidation. Enhanced formation of F(2)-iPs, together with increased in vivo platelet activation, has been reported in association with several cardiovascular risk factors. Thus, it has been suggested that F(2)-iPs may transduce oxidant stress-dependent platelet activation. Measurements of 8-iso-PGF(2alpha), an abundant F(2)-iP formed in vivo, in urine may provide sensitive biochemical end-points for the assessment of the oxidant status of the patient and the true efficacy of anti-oxidant therapies. The incorporation of such biochemical end-points in clinical trials may help to verify the reliability of the oxidative modification hypothesis in the development of atherosclerosis.
多条证据表明，活性氧在血管病变的发展中起作用，包括那些定义动脉粥样硬化、高血压和血管成形术后再狭窄的病变。抗氧化剂前瞻性临床试验中出现的混乱情况可能反映出，在招募合适患者以及指导选择待测试抗氧化剂的合适剂量方面，传统脂质过氧化指标存在不足。体外氧化应激指标在评估体内脂质过氧化的实际速率时，其准确性可能存疑。F(2)-异前列腺素（F(2)-iPs）是通过自由基催化攻击酯化花生四烯酸非酶促形成的，其测量为识别脂质过氧化速率增加的人群提供了可靠工具。据报道，F(2)-iPs的生成增加，以及体内血小板活化增加，与多种心血管危险因素有关。因此，有人提出F(2)-iPs可能介导氧化应激依赖性血小板活化。测量尿液中8-异前列腺素F(2α)（一种在体内大量形成的F(2)-iP），可能为评估患者的氧化状态和抗氧化治疗的真正疗效提供敏感的生化终点。在临床试验中纳入此类生化终点可能有助于验证氧化修饰假说在动脉粥样硬化发展中的可靠性。
