胡园 翟宝祺 陶磊 赵海荣 张成桂 张瑱 肖怀 赵昱

【摘 要】 目的：考察蜜蜂蜂毒（Bee Venom，BV）经皮下注射对正常家兔血小板聚集性和粘附性的影响。方法：正常家兔连续皮下注射给药5 d，末次给药后1.5 h心脏取血，二磷酸腺苷（Adenosine diphosphate， ADP）、胶原（Collagen，COL）诱导家兔血小板聚集，采用比浊法检测血小板聚集率，并使用血小板聚集仪测定富血小板血浆（Platelet rich plasma，PRP）OD值、计算粘附率。结果：BV对血小板聚集率的影响实验结果显示，与生理盐水组比较，BV 0.18、0.36、0.72 mg/kg·BW剂量组，均可对ADP诱导的血小板聚集产生抑制作用，其聚集率分别为47.70±3.18、43.10±13.21、29.80±14.30，差异具有统计学意义（P<0.05），其抑制率分别为26.54%、36.62%、51.11%，且呈量效依赖关系；BV 0.36、0.72 mg/kg·BW剂量组，可对COL诱导的血小板聚集产生抑制作用，其聚集率分别为47.62±14.65、28.72±13.34（P<0.05），抑制率分别为29.28%、62.90%。血小板粘附实验显示，在COL诱导下，BV中、高剂量组均能降低COL诱导的血小板聚集率（P<0.05）；粘附抑制率分别为43.94%、49.36%。结论：BV对ADP、COL诱导的家兔血小板聚集有一定的抑制作用，亦可以抑制血小板在胶原表面的粘附。

【关键词】 蜜蜂蜂毒；血小板聚集；血小板粘附

【中图分类号】R-332 【文献标志码】 A【文章编号】1007-8517（2018）13-009-04

Abstract：Objective To investigate the effects of bee venom （BV） on normal rabbit platelet aggregation and the adhesion function.Methods After continuously administrating study agents to normal rabbits for 5 days， blood samples were drawn from rabbits hearts after 1.5 h of the last administration. Turbidimetric method was used to determine the platelet aggregation rates with adenosine diphosphate （ADP） and collagen （COL） as inducers. The platelet aggregation analyzer AggRAM was adopted to measure the OD values of platelet-rich plasma（Platelet rich plasma，PRP） in study rabbits and the adhesion rates were generated thereafter. Results The platelet aggregation rates showed that BV at the doses of 0.18， 0.36， 0.72 mg/kg·BW could inhibit ADP-induced platelet aggregation whose platelet aggregation rate is 47.70±3.18、43.10±13.21、29.80±14.30when compared with NS group， and their inhibition rates were 26.54%， 36.6%， 51.11%， respectively. The difference was statistically significant with a dose-dependent manner. BV 0.36 and 0.72 mg/kg·BW dose groups could significantly inhibit COL-induced platelet aggregation whose platelet aggregation rate is 47.62±14.65、28.72±13.34 with inhibition rates of 29.28%， 62.90%， respectively. Platelet adhesion assay showed that COL-induced platelet aggregation rates were significantly decreased in BV middle- and high-dose groups （P<0.05） with the corresponding inhibition rates of 43.94% and 49.36%， respectively.Conclusion The bee venom possessed a certain inhibitory effect on ADP， COL-induced platelet aggregation in rabbits， could also inhibit platelet adhesion on the collagen surface.

Keywords：Bee Venom； Platelet Aggregation； Platelet Adhesion

脑血管疾病是全身性血管病变或系统性血管病在脑部的表现，是血管源性脑部病损的总称，中医称“中风”，具有发病率高、病死率高、致残率高和复发率高的特点，严重影响人们的健康以及社会經济的发展[1]。目前临床上常用的预防和治疗缺血性脑血管疾病的药物有溶栓、抗凝和抗血小板聚集药[2]，其中抗血小板治疗是缺血性脑卒中二级预防的重要手段[3]。因此，低毒副作用、可长期使用的抗血小板聚集药物的开发是当前防治脑血管疾病药物研发的热点之一。

动物毒素，如水蛭[4]、蚯蚓[5]、蛛毒[6]、蛇毒[7]，及昆虫毒素[8-9]等具有明显的抗血栓作用。蜜蜂蜂毒由蜜蜂的毒腺分泌并贮存于毒囊中，是一种成分复杂且药理作用较多的无色芳香液体[10]，研究发现，其具有很强的抗凝血[11]及抗血栓[12]作用，能使血液凝固时间明显延长。……