Suzuki Tomo, Kamio Yoshinobu, Makino Hiroshi, Hokamura Kazuya, Kimura Tetsuro, Yamasaki Tomohiro, Hiramatsu Hisaya, Umemura Kazuo, Namba Hiroki
Department of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Cerebrovasc Dis. 2018;45(3-4):180-186. doi: 10.1159/000487812. Epub 2018 Apr 3.
Subarachnoid hemorrhage (SAH) from intracranial aneurysm rupture results in significant morbidity and mortality. In the present study, we examined the effect of most widely used antiplatelet drugs, aspirin and cilostazol, on aneurysm rupture prevention using a mouse intracranial aneurysm model.
Intracranial aneurysms were induced by a combination of deoxycorticosterone acetate-salt and a single injection of elastase into the cerebrospinal fluid in mice. Treatment with aspirin or cilostazol was started 1 day after aneurysm induction. Aneurysm rupture was detected by neurological symptoms and the presence of intracranial aneurysm with SAH was confirmed by post-mortem examination.
Aspirin (10 mg/kg) significantly reduced aneurysm rupture (control:aspirin = 80%:31%, p < 0.05) without affecting the overall incidence of aneurysm formation (60%:62%). Cilostazol (3 mg/kg, 30 mg/kg) did not reduce both rupture rate (control:3 mg/kg:30 mg/kg = 81%:67%:77%) and the overall incidence of aneurysm formation (control:3 mg/kg:30 mg/kg = 72%:71%:76%). Tail vein bleeding time prolonged significantly in both aspirin and cilostazol groups (p < 0.01).
Aspirin prevented aneurysm rupture in a mouse intracranial aneurysm model, while cilostazol did not. Aspirin, the most frequently used drug for patients with ischemic myocardial and cerebral diseases, is also effective in preventing cerebral aneurysmal rupture.
颅内动脉瘤破裂导致的蛛网膜下腔出血（SAH）会造成显著的发病率和死亡率。在本研究中，我们使用小鼠颅内动脉瘤模型，研究了最常用的抗血小板药物阿司匹林和西洛他唑对预防动脉瘤破裂的作用。
通过醋酸脱氧皮质酮 - 盐联合向小鼠脑脊液单次注射弹性蛋白酶诱导颅内动脉瘤。在动脉瘤诱导后1天开始用阿司匹林或西洛他唑进行治疗。通过神经症状检测动脉瘤破裂，并通过尸检确认伴有SAH的颅内动脉瘤的存在。
阿司匹林（10mg/kg）显著降低了动脉瘤破裂率（对照组：阿司匹林组 = 80%：31%，p < 0.05），且不影响动脉瘤形成的总体发生率（60%：62%）。西洛他唑（3mg/kg，30mg/kg）既未降低破裂率（对照组：3mg/kg：30mg/kg = 81%：67%：77%），也未降低动脉瘤形成的总体发生率（对照组：3mg/kg：30mg/kg = 72%：71%：76%）。阿司匹林组和西洛他唑组的尾静脉出血时间均显著延长（p < 0.01）。
在小鼠颅内动脉瘤模型中，阿司匹林可预防动脉瘤破裂，而西洛他唑则不能。阿司匹林是缺血性心肌和脑部疾病患者最常用的药物，在预防脑动脉瘤破裂方面也有效。
