Department of Basic Medical Sciences, School of Veterinary Medicine, Center for Paralysis Research, Purdue University, West Lafayette, Indiana 47907, USA.
J Neurochem. 2009 Dec;111(6):1348-56. doi: 10.1111/j.1471-4159.2009.06395.x. Epub 2009 Sep 23.
It has long been established that oxidative stress plays a critical role in the pathophysiology of spinal cord injury, and represents an important target of therapeutic intervention following the initial trauma. However, free radical scavengers have been largely ineffective in clinical trials, and as such a novel target to attenuate oxidative stress is highly warranted. In addition to free radicals, peroxidation of lipid membranes following spinal cord injury (SCI) produces reactive aldehydes such as acrolein. Acrolein is capable of depleting endogenous antioxidants such as glutathione, generating free radicals, promoting oxidative stress, and damaging proteins and DNA. Acrolein has a significantly longer half-life than the transient free radicals, and thus may represent a potentially better target of therapeutic intervention to attenuate oxidative stress. There is growing evidence, from our lab and others, to suggest that reactive aldehydes such as acrolein play a critical role in oxidative stress and SCI. The focus of this review is to summarize the cellular and biochemical mechanisms of acrolein-induced membrane damage, mitochondrial injury, oxidative stress, cell death, and functional loss. Evidence will also be presented to suggest that acrolein scavenging may be a novel means of therapeutic intervention to attenuate oxidative stress and improve recovery following traumatic SCI.
长期以来，氧化应激在脊髓损伤的病理生理学中起着关键作用，并且是创伤后治疗干预的重要靶点。然而，自由基清除剂在临床试验中基本上没有效果，因此，减轻氧化应激的新靶点是非常必要的。除了自由基之外，脊髓损伤后脂质膜的过氧化会产生丙烯醛等反应性醛。丙烯醛能够耗尽内源性抗氧化剂如谷胱甘肽，产生自由基，促进氧化应激，并损伤蛋白质和 DNA。丙烯醛的半衰期比瞬态自由基长得多，因此可能是减轻氧化应激的治疗干预的一个潜在更好的靶点。越来越多的证据表明，丙烯醛等反应性醛在氧化应激和 SCI 中起着关键作用。这篇综述的重点是总结丙烯醛诱导的膜损伤、线粒体损伤、氧化应激、细胞死亡和功能丧失的细胞和生化机制。还将提出证据表明，丙烯醛清除可能是一种减轻氧化应激和改善创伤性 SCI 后恢复的新的治疗干预手段。
