Murakami Masaji, Fujioka Shodo, Hirata Yoshifumi, Kuratsu Jun-Ichi
Department of Neurosurgery, Kumamoto Takumadai Hospital, Kumamoto, Japan.
J Stroke Cerebrovasc Dis. 2008 Jan-Feb;17(1):16-22. doi: 10.1016/j.jstrokecerebrovasdis.2007.09.005.
Statins, 3-hydroxy-3-methylglutaryl-coenzymeA reductase inhibitors, have pleiotropic effects that are independent of their cholesterol-lowering activities. For example, they improve vascular endothelial function and exert anti-inflammatory effects. In large clinical trials they reduced the incidence of stroke and myocardial infarction; however, little is currently known regarding the mechanism or mechanisms underlying their clinically confirmed stroke protection.
We assessed 10 patients who had experienced a stroke at least 6 months earlier; they received low-dose (5 mg) simvastatin. Using our triple-injection technetium 99m-ethylcysteinate dimer method, we determined their cerebral blood flow and cerebrovascular reactivity. A second assessment of at-rest cerebral blood flow and cerebrovascular reactivity was performed 4 or more months (mean 6 months) after the start of statin administration. We used acetazolamide (1 g) as the vasodilator. The region of interest was the middle cerebral artery territory on a 3-dimensional stereotaxic region of interest template.
Statin administration did not significantly affect the regional cerebral blood flow at rest. Before statin treatment, the patients' vasoreactivity, determined by the triple-injection technetium 99m-ethylcysteinate dimer method, demonstrated delayed, poor, or near-normal response patterns. Statin treatment improved vasoreactivity in all patients. Their mean serum total cholesterol level before statin administration was 200 mg/dL (range 187-256 mg/dL). Statin treatment significantly reduced their mean serum total cholesterol to 180 mg/dL (range 128-220 mg/dL) (P < .01).
The clinically confirmed stroke protection activity exerted by statins may be attributable to improved cerebrovascular reactivity.
他汀类药物,即3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂,具有多种独立于其降胆固醇活性的作用。例如,它们可改善血管内皮功能并发挥抗炎作用。在大型临床试验中,它们降低了中风和心肌梗死的发生率;然而,目前对于其临床证实的中风保护作用的潜在机制知之甚少。
我们评估了10例至少在6个月前发生过中风的患者;他们接受低剂量(5毫克)辛伐他汀治疗。使用我们的三重注射锝99m - 乙基半胱氨酸二聚体方法,我们测定了他们的脑血流量和脑血管反应性。在开始使用他汀类药物治疗4个月或更长时间(平均6个月)后,对静息脑血流量和脑血管反应性进行了第二次评估。我们使用乙酰唑胺(1克)作为血管扩张剂。感兴趣的区域是三维立体定向感兴趣区域模板上的大脑中动脉区域。
服用他汀类药物对静息时的局部脑血流量没有显著影响。在他汀类药物治疗前,通过三重注射锝99m - 乙基半胱氨酸二聚体方法测定的患者血管反应性显示出延迟、不良或接近正常的反应模式。他汀类药物治疗改善了所有患者的血管反应性。他们在服用他汀类药物前的平均血清总胆固醇水平为200毫克/分升(范围为187 - 256毫克/分升)。他汀类药物治疗使他们的平均血清总胆固醇显著降低至180毫克/分升(范围为128 - 220毫克/分升)(P <.01)。
他汀类药物临床证实的中风保护活性可能归因于改善的脑血管反应性。