Suzuka H, Fujiwara H, Tanaka M, Yoshifusa H, Nakamura Y, Shibata Y
Yamashina Laboratories, Nippon Shinyaku Co., Ltd, Kyoto, Japan.
J Cardiovasc Pharmacol. 1995 Jan;25(1):9-13. doi: 10.1097/00005344-199501000-00003.
We examined the antithrombotic effect of ticlopidine on occlusive thrombi of small coronary arteries in (NZWxBXSB)F1 [(WxB)F1] male mice with myocardial infarction (MI) and systemic lupus erythematosus (SLE). Ticlopidine (3 and 10 mg/kg) was given to the mice as an additive to a standard laboratory diet from the time the mice were aged 16-24 weeks. The higher dose of ticlopidine significantly increased survival rate of the mice. In mice that received 10 mg/kg ticlopidine, the incidence of MI, the percentage of MI area (%MI), and the incidence and number of small coronary arteries with significant stenosis were significantly lower than in controls. The stenosed lesions were divided into occlusive thrombi related to acute MI and intimal thickening related to old MI. No mice had evidence of significant stenosis or thrombosis in the extramyocardial coronary arteries. Glomerulonephritis, blood urea nitrogen (BUN), and circulating immune complexes were not significantly different among the three groups. A high dose of ticlopidine prevented small coronary artery disease and MI and increased the survival of (WxB)F1 male mice, suggesting that this agent has an antithrombotic effect on occlusive thrombi of the small coronary arteries in such mice.
我们研究了噻氯匹定对患有心肌梗死(MI)和系统性红斑狼疮(SLE)的(新西兰白兔×近交系B×近交系SB)F1 [(W×B)F1]雄性小鼠小冠状动脉闭塞性血栓的抗血栓形成作用。从16 - 24周龄开始,将噻氯匹定(3和10 mg/kg)作为标准实验室饮食的添加剂给予小鼠。较高剂量的噻氯匹定显著提高了小鼠的存活率。在接受10 mg/kg噻氯匹定的小鼠中,MI的发生率、MI面积百分比(%MI)以及小冠状动脉显著狭窄的发生率和数量均显著低于对照组。狭窄病变分为与急性MI相关的闭塞性血栓和与陈旧性MI相关的内膜增厚。没有小鼠在心肌外冠状动脉中有显著狭窄或血栓形成的证据。三组之间的肾小球肾炎、血尿素氮(BUN)和循环免疫复合物没有显著差异。高剂量的噻氯匹定可预防小冠状动脉疾病和MI,并提高(W×B)F1雄性小鼠的存活率,表明该药物对此类小鼠小冠状动脉闭塞性血栓具有抗血栓形成作用。