乌苏里藜芦生物碱单体计米丁的抗动脉血栓作用

Study on anti-arterial thrombosis effect of germidine,an alkaloid isolated from veratrum nigrum L.var ussuriense Nakai

关键词:  乌苏里藜芦生物碱  计米丁  动脉血栓  血小板聚集

Key words:  veratrum nigrum L.var ussuriense Nakai alkaloid  germidine  arterial thrombosis  platalet aggregation

摘要:

［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，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（1.3～20.0 μg·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（2.5～20.0 μg·kg^-1）及体外（6.3～50.0 μg·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29.3 μg·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。

Abstract:

［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 maximum platelet aggregation rates were tested after dosing.Then,the decreasing percentage of platelet aggregation rate was calculated 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.