Vaughan C J, Delanty N, Basson C T
Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, New York, New York, USA.
CNS Drugs. 2001;15(8):589-96. doi: 10.2165/00023210-200115080-00002.
An emerging body of evidence indicates that beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or 'statins', provide neuroprotection in addition to reducing ischaemic stroke. Statins reduce the incidence of ischaemic stroke by stabilising atherosclerotic plaques in the precerebral vasculature and through antithrombotic actions, and the neuroprotective effects of statins may confer significant clinical benefit. Some of these neuroprotective effects are likely to be cholesterol independent and mediated by the interruption of isoprenoid biosynthesis. Therapy with statins may modulate endothelial function and preserve blood flow to regions exposed to an ischaemic insult. In particular, statin-mediated preservation of endothelial nitric oxide synthase activity in cerebral vasculature, especially in the ischaemic penumbra, may limit neurological deficit. Moreover, putative anti-inflammatory and antioxidant properties of statins may confer additional neuroprotection. Further large clinical trials are necessary to address the role of statin therapy in the primary prevention of stroke, small vessel cerebrovascular disease and vascular dementia.
越来越多的证据表明,β-羟基-β-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂,即“他汀类药物”,除了能减少缺血性中风外,还具有神经保护作用。他汀类药物通过稳定脑前血管中的动脉粥样硬化斑块以及通过抗血栓作用来降低缺血性中风的发生率,并且他汀类药物的神经保护作用可能带来显著的临床益处。这些神经保护作用中的一些可能与胆固醇无关,而是由类异戊二烯生物合成的中断介导的。他汀类药物治疗可能调节内皮功能并维持流向遭受缺血性损伤区域的血流。特别是,他汀类药物介导的脑血管内皮型一氧化氮合酶活性的维持,尤其是在缺血半暗带,可能会限制神经功能缺损。此外,他汀类药物假定的抗炎和抗氧化特性可能会提供额外的神经保护作用。有必要进行进一步的大型临床试验,以确定他汀类药物治疗在中风、小血管脑血管疾病和血管性痴呆的一级预防中的作用。