Department of Neuroscience, University of California San Diego, 9500 Gilman Drive MTF316, La Jolla, CA 92093-0624, USA.
Brain Res. 2009 Dec 15;1303:144-50. doi: 10.1016/j.brainres.2009.09.064. Epub 2009 Sep 23.
Statins were designed as cholesterol-lowering drugs for the prevention of coronary artery disease. It is estimated that there are currently 33.5 million U.S. patients on chronic statin treatment regimens. Recently, statins have been shown to have pleiotropic including anti-inflammatory and neuroprotective effects. In this study, we assessed the pharmacological effects of simvastatin administered alone and in combination with tissue plasminogen activator (tPA) on measures of ischemia and hemorrhage in large clot embolized New Zealand white rabbits. For these studies, simvastatin (20 mg/kg, SC in DMSO) was administered 24 and 4 h prior to large clot embolization in order to achieve a "loading dose" pretreatment with the drug. In combination studies, tPA (3.3 mg/kg, IV) was administered 1 h following embolization. Intravenous tPA administration significantly increased hemorrhage volume by 175% (p=0.015) and hemorrhage incidence by 60% (p>0.05) compared to control, but did not affect infarct incidence or volume. Simvastatin treatment significantly decreased tPA-induced hemorrhage incidence (p=0.022) and volume (p=0.0001) following embolization. The study suggests that simvastatin treatment blocks or attenuates mechanisms involved in tPA-induced hemorrhage. Based upon our results, patients on simvastatin treatment may have significantly reduced tPA-induced side effects should they require tPA administration following an embolic stroke.
他汀类药物最初是作为降低胆固醇的药物用于预防冠状动脉疾病的。据估计，目前美国有 3350 万名慢性他汀类药物治疗患者。最近，他汀类药物已被证明具有多种作用，包括抗炎和神经保护作用。在这项研究中，我们评估了辛伐他汀单独给药和与组织型纤溶酶原激活物（tPA）联合给药对新西兰大白兔大栓子栓塞后缺血和出血的影响。为了进行这些研究，在大栓子栓塞前 24 小时和 4 小时给予辛伐他汀（20mg/kg，皮下注射于 DMSO 中）以实现药物的“负荷剂量”预处理。在联合研究中，在栓塞后 1 小时给予 tPA（3.3mg/kg，静脉内）。与对照组相比，静脉内 tPA 给药使出血体积增加了 175%（p=0.015），出血发生率增加了 60%（p>0.05），但不影响梗死发生率或体积。辛伐他汀治疗显著降低了栓塞后 tPA 诱导的出血发生率（p=0.022）和体积（p=0.0001）。研究表明，辛伐他汀治疗可阻断或减弱 tPA 诱导出血的机制。根据我们的结果，接受辛伐他汀治疗的患者在发生栓塞性中风后需要 tPA 治疗时，可能会显著减少 tPA 引起的副作用。
