Department of Internal Medicine, Cardiology and Angiology, Richard-Thoma-Laboratories for Arteriogenesis, Center for Cardiovascular Research and Experimental and Clinical Research Center, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
J Cereb Blood Flow Metab. 2012 Jan;32(1):105-14. doi: 10.1038/jcbfm.2011.113. Epub 2011 Aug 10.
This study investigated the effects of acetylsalicylic acid (ASA) and clopidogrel, standardly used in the secondary prevention of vascular occlusions, on cerebral arteriogenesis in vivo and in vitro. Cerebral hypoperfusion was induced by three-vessel occlusion (3-VO) in rats, which subsequently received vehicle, ASA (6.34 mg/kg), or clopidogrel (10 mg/kg). Granulocyte colony-stimulating factor (G-CSF), which enhanced monocyte migration in an additional cell culture model, augmented cerebrovascular arteriogenesis in subgroups (40 μg/kg). Cerebrovascular reactivity and vessel diameters were assessed at 7 and 21 days. Cerebrovascular reserve capacity was completely abolished after 3-VO and remained severely compromised after 7 (-14±14%) and 21 (-5±11%) days in the ASA groups in comparison with controls (4±5% and 10±10%) and clopidogrel (4±13% and 10±8%). It was still significantly decreased when ASA was combined with G-CSF (1±4%) compared with G-CSF alone (20±8%). Posterior cerebral artery diameters confirmed these data. Monocyte migration into the vessel wall, improved by G-CSF, was significantly reduced by ASA. Acetylsalicylic acid, but not clopidogrel, inhibits therapeutically augmented cerebral arteriogenesis.
本研究旨在探讨乙酰水杨酸（ASA）和氯吡格雷这两种常用于血管闭塞二级预防的药物，对体内和体外脑动脉生成的影响。通过三血管闭塞（3-VO）在大鼠中诱导脑灌注不足，随后给予载体、ASA（6.34mg/kg）或氯吡格雷（10mg/kg）。粒细胞集落刺激因子（G-CSF）在另一个细胞培养模型中增强单核细胞迁移，在亚组中增强脑血管动脉生成（40μg/kg）。在第 7 天和第 21 天评估脑血管反应性和血管直径。与对照组（4±5%和 10±10%）和氯吡格雷组（4±13%和 10±8%）相比，3-VO 后脑血管储备能力完全丧失，在 ASA 组中在第 7 天（-14±14%）和第 21 天（-5±11%）仍然严重受损，并且当 ASA 与 G-CSF 联合使用时（1±4%）与单独使用 G-CSF 相比（20±8%）仍然显著降低。这些数据通过大脑后动脉直径得到证实。G-CSF 改善的单核细胞向血管壁迁移，被 ASA 显著减少。ASA 抑制了治疗性增强的脑动脉生成，而氯吡格雷则没有。
