西洛他唑对小鼠局灶性持续脑缺血的保护作用  

Protective effect of cilostazol on persistent focal cerebral ischemia in mice

作　　者：徐慧敏[1,2] 叶夷露[1] 史文珍[1] 陈丽萍[1] 张纬萍[1] 魏尔清[1] 

机构地区：[1]浙江大学医学院药理学教研室 [2]浙江大学医学院附属第二医院药剂科,杭州310009

出　　处：《中国新药杂志》2007年第12期947-950,共4页Chinese Journal of New Drugs

摘　　要：目的:观察磷酸二酯酶3抑制剂西洛他唑对小鼠持续性局灶性脑缺血的保护作用,探讨其有效剂量和治疗时间窗。方法:以大脑中动脉阻塞诱导小鼠持续性局灶性脑缺血。缺血前30 min腹腔注射不同剂量的西洛他唑(0．3～30 mg·kg^(-1)),以普鲁司特(0．1 mg·kg^(-1))作为阳性对照;观察药物对缺血后神经功能缺损症状、脑梗死体积、两侧大脑半球比值、IgG渗出的影响。在另一批小鼠,分别在缺血后1,2和3 h腹腔注射西洛他唑10 mg·kg^(-1),观察药物对上述指标(除IgG渗出)的影响。结果:缺血前30 min注射西洛他唑3,10 mg·kg^(-1)及普鲁司特,均能减轻缺血后24 h的神经症状、减小脑梗死体积、减轻脑水肿和IgG的渗出;缺血1和2 h内给予西洛他唑10 mg·kg^(-1),对上述指标有显著抑制作用。结论:西洛他唑对急性脑缺血损伤有保护作用,其有效剂量为3～10 mg·kg^(-1),治疗时间窗为缺血后2 h。Objective： To determine the dose- and time-dependent protective effect of cilostazol, a phosphodiesterase 3 inhibitor, on focal cerebral ischemia in mice. Methods： Persistent focal cerebral ischemia was induced by middle cerebral artery occlusion（MCAO）. Various doses of cilostazol（0.3 - 30 mg· kg^ -1 ） and a positive control drug pranlukast （0. 1 mg· kg^ -1 ） were ip injected 30 min before MCAO, The neurological deficits, infarct volume, brain edema, and IgG exudation were determined 24 h after MCAO. In addition, the effect on ischemic injuries was also evaluated when cilostazol was ip injected 1, 2 and 3 h after MCAO. Results： Cilostazol（3 and 10 mg· kg^ -1 ）and pranlukast（0. 1mg· kg^ -1 ）injected 30 min before MCAO significantly reduced the neurological deficits, infarct volume, brain edema, and IgG exudation. On the other hand, cilostazol（ 10 mg· kg^ -1 , ip injected 1 and 2 h after MCAO） signif- icantly reduced the neurological deficits, infarct volume and brain edema. Conclusion： Cilostazol has the protective effect on focal cerebral ischemia in mice. The effective doses are 3 - 10 mg· kg^ -1 , and the therapeutic window is within 2 h after ischemia.

关 键 词：西洛他唑 脑缺血 磷酸二酯酶3抑制剂 

分 类 号：R743.31[医药卫生—神经病学与精神病学] R976[医药卫生—临床医学]