[目的]探讨乌苏里藜芦生物碱单体计米丁(germidine)抗动脉血栓形成作用的机制。[方法]大鼠70只,随机分为7组:生理盐水(NS)组、计米丁5个剂量组和阳性对照药物赖氨匹林(LAS)组。测定各组大鼠给药后血流阻塞时间(OT),以NS组为基准,计算不同给药组OT延长百分率。采用Born法评价计米丁的体内、外血小板聚集抑制活性。大鼠60只,随机分为6组:NS组,计米丁4个剂量组,以及阳性对照药物LAS组。大鼠给药后取血,制备富血小板血浆(PRP)和贫血小板血浆(PPP)。测定ADP诱导的血小板5 min最大聚集率。以NS组为基准,计算不同给药组血小板聚集抑制百分率。另取大鼠60只,随机分为6组:NS组,计米丁4个剂量组,和阳性对照药物赖氨匹林(LAS)组。取血,制备PRP和PPP,于PRP中分别加入不同浓度受试药物或NS。测定ADP诱导的血小板5min最大聚集率。以NS组为基准,计算不同给药组血小板聚集抑制百分率,并计算计米丁体外抑制血小板聚集的半数抑制浓度IC50。[结果]与NS组相比,大鼠静脉注射计米丁(1.3-20.0μg.kg^-1)后呈剂量依赖性OT延长,计米丁呈剂量依赖性地抑制大鼠体内(2.5-20.0μg.kg^-1)及体外(6.3-50.0μg.L-1)血小板最大聚集率,其体外抑制血小板聚集的半数抑制浓度IC50为29.3μg.L-1。[结论]计米丁具有抗动脉血栓形成作用,该作用与其抗血小板作用有关。
[Objective] To study the effect of germidine against arterial thrombosis in rats as well as the possible mechanism.[Methods] Seventy rats were divided into 7 groups randomly: NS group,5 groups with different doses and positive control group(LAS).Occlusion time(OT) was measured after dosing.Then,the OT increasing percentage of germidine-treated groups,according to OT of saline control group,was served as an index to evaluate anti-arterial thrombosis effects of the drug.Born’s turbidimetric method was used to examine the platelet aggregation inhibitory activity of germidine in vitro and in vivo.Then,60 rats were divided into 6 groups randomly: NS group,4 groups with different doses and LAS group. The blood was drawn to prepare platelet rich plasma (PRP) and platelet poor plasma (PPP). ADP - induced 5 min maxi- mum platelet aggregation rates were tested after dosing. Then, the decreasing percentage of platelet aggregation rate was cal- culated according to that of NS group. Other 60 rats were divided into 6 groups randomly : NS group ,4 groups with different doses and LAS group. PRP and PPP were obtained, different concentration of test drugs or saline were added into PRP, then ADP - induced 5 min maximum platelet aggregation rate were tested, finally the decreasing percentage of platelet aggregation rate was calculated compared with NS group, as well as IC50 was calculated. [ Results] In comparison with rats in NS group, the rats administered in 5 different doses ( 1.3 - 20.0 μg.kg^-1) of germidine showed significantly and dose - dependently prolonged occlusion time (OT) of carotid artery injured by electrical stimulation, and platelet aggregation was found to be inhibited by germidine dose - dependently,in both in vitro and in vivo. [ Conclusion ] Germidine has anti - arterial thrombosis effect,which is related to its potent platelet aggregation inhibitory activity.