Heath M F, Evans R J, Hayes L J
University of Cambridge, Department of Clinical Veterinary Medicine, UK.
Equine Vet J. 1998 Sep;30(5):408-11. doi: 10.1111/j.2042-3306.1998.tb04510.x.
Dextrans of mean molecular weight 70 kDa (dextran-70) have had clinical use as anti-thrombotics in man. A major part of the anti-thrombotic action is mediated via inhibition of platelet function. Greatorex (1975, 1977) treated thromboembolic colic in horses with infusions of dextran-70 and reported a 90% recovery rate, but this treatment is nonetheless rarely used. We have used an in vitro method to examine the effect of dextran-70 on equine platelet suspensions, in the hope that understanding the mechanism of action of dextran-70 might lead to the development of alternative therapeutic agents. The effects of dextran-70 on equine platelets occurred immediately in vitro with an initial activation and shape change. Subsequent assessment of aggregation revealed a dose-dependent specific inhibition of platelet-activating factor (PAF)-induced aggregation, significant in rate of aggregation at dextran-70 concentrations >40 g/l (P<0.05) and in extent of aggregation at dextran-70 concentrations >50 g/l (P<0.05). Pre-incubation with 60 g/l dextran-70 significantly inhibited the rate and extent of aggregation in response to PAF (1 nmol/l) (P<0.001 and P = 0.003, respectively) but this was not dependent on the duration of pre-incubation (from 0 to 150 min). No effects were seen when the agonist was adenosine 5'-diphosphate (200 nmol/l), collagen (10 mg/l), 5-hydroxytryptamine (100 micromol/l) or U44069 (600 nmol/l) (all P>0.1). Analysis of PAF concentration-aggregation curves after pre-incubation with 60 g/l dextran-70 indicated significant noncompetitive inhibition by dextran-70 (P<0.001 for rate and extent of aggregation). The ability of dextran-70 to inhibit responses of equine platelets to PAF is probably an important component of its beneficial effect as an anti-thrombotic in colic cases.
平均分子量为70 kDa的葡聚糖（葡聚糖-70）已在人体中作为抗血栓药物用于临床。其抗血栓作用的主要部分是通过抑制血小板功能介导的。Greatorex（1975年、1977年）用葡聚糖-70输注治疗马的血栓性绞痛，并报告治愈率为90%，但这种治疗方法仍然很少使用。我们使用体外方法研究葡聚糖-70对马血小板悬液的影响，希望了解葡聚糖-70的作用机制可能会导致开发替代治疗药物。葡聚糖-70对马血小板的作用在体外立即发生，伴有初始激活和形状改变。随后对聚集的评估显示，对血小板活化因子（PAF）诱导的聚集有剂量依赖性的特异性抑制，在葡聚糖-70浓度>40 g/l时聚集速率显著受抑制（P<0.05），在葡聚糖-70浓度>50 g/l时聚集程度显著受抑制（P<0.05）。用60 g/l葡聚糖-70预孵育显著抑制了对PAF（1 nmol/l）的聚集速率和程度（分别为P<0.001和P = 0.003），但这并不取决于预孵育时间（从0到150分钟）。当激动剂为5'-二磷酸腺苷（200 nmol/l）、胶原（10 mg/l）、5-羟色胺（100 μmol/l）或U44069（600 nmol/l）时未观察到影响（所有P>0.1）。用60 g/l葡聚糖-70预孵育后对PAF浓度-聚集曲线的分析表明，葡聚糖-70有显著的非竞争性抑制作用（聚集速率和程度P<0.001）。葡聚糖-70抑制马血小板对PAF反应的能力可能是其在绞痛病例中作为抗血栓药物产生有益作用的一个重要组成部分。
