【摘 要】
：
[目的]通过角叉菜胶诱导的大鼠模型来探讨阿司匹林丁香酚酯(AEE)对血栓形成的预防作用.通过血常规、血凝参数、体外抗凝实验及血小板聚集率来说明药物的作用机制.[方法[采用0.5％的羧甲基纤维素钠(CMC-Na)制备AEE悬浮液,大鼠按18、36和72 mg/kg的剂量灌胃给药七天,腹腔注射20 mg/kg的角叉菜胶诱导尾部血栓.为明确AEE和其前体化合物之间的区别,阿司匹林(Asp,20 mg/k
【机 构】
：
中国农业科学院兰州畜牧与兽药研究所农业部兽用药物创制重点实验室/甘肃省新药工程重点实验室,甘肃兰州730050
【出 处】
：
中国畜牧兽医学会兽医药理毒理学分会第十一届会员代表大会暨第十三次学术讨论会与中国毒理学会兽医毒理专业委员会第五次学术研讨
论文部分内容阅读
[目的]通过角叉菜胶诱导的大鼠模型来探讨阿司匹林丁香酚酯(AEE)对血栓形成的预防作用.通过血常规、血凝参数、体外抗凝实验及血小板聚集率来说明药物的作用机制.[方法[采用0.5％的羧甲基纤维素钠(CMC-Na)制备AEE悬浮液,大鼠按18、36和72 mg/kg的剂量灌胃给药七天,腹腔注射20 mg/kg的角叉菜胶诱导尾部血栓.为明确AEE和其前体化合物之间的区别,阿司匹林(Asp,20 mg/kg)、丁香酚(Eug,18 mg/kg)及Asp和Eug结合给药(Asp： 20 mg/kg；Eug： 18 mg/kg)作为药物对照.CMC-Na (30 mg/kg)作为溶剂对照.角叉菜胶注射后测量24 h和48 h大鼠尾部血栓的长度,最后一次测量后,麻醉采血,测定相关参数.血小板聚集率采用Born法测定,二甲基亚砜(DMSO)作为溶剂对照组,以ADP (5 μM)为诱导剂,最大聚集率为观测值记录血小板聚集率.体外抗凝实验将不同浓度的药物添加到新鲜大鼠血液中,37℃孵育30 min,观察抗凝效果.[结果]实验结果表明,AEE能够显著降低大鼠尾部血栓的长度.相比于模型组和溶剂对照组,AEE组尾部血栓明显较短(P＜0.01).同时于Asp组、Eug组和Asp+Eug组也存在显著差别(P＜0.01).凝血参数实验结果表明AEE可引起凝血酶原时间和凝血酶时间的改变,降低纤维蛋白原的含量.血常规实验说明角叉菜胶诱导的血栓模型可引起白细胞、中性粒细胞的显著升高和血小板的降低.在给药组,相关指标并未明显改变.红细胞、红细胞比容及血小板在AEE给药组相比于溶剂组明显降低.体外血小板聚集率实验表明AEE可显著抑制血小板聚集,相比于等摩尔量的Asp,其抗血小板聚集的效果较差.体外抗凝实验结果表明AEE无抗凝效果.[结论]AEE能够显著抑制角叉菜胶诱导的大鼠尾部血栓的形成,同时其作用效果强于Asp、Eug和Asp+Eug.AEE可能通过抑制血小板聚集,降低纤维蛋白原含量,改变凝血参数等来抑制血栓的形成.
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