放化疗细胞保护剂WR-2721对国人血小板功能影响的研究

目的 探讨放、化疗细胞保护剂WR -2721对生理性激活剂ADP 、胶原和血小板激活因子(PAF)引起的血小板激活的影响。方法 取20 ~ 35岁健康人血液,分别给予生理性激活剂ADP 1 μmol·L^-1 、胶原2 mg·L^-1和PAF 0.1 mg·L^-1后,再用终浓度为10^-7 ~ 10^-5 mol·L^-1的WR-2721 处理,观察对血小板聚集的影响,然后观察血栓素B₂(TXB₂)和NO 的水平。结果 WR-2721 抑制ADP 、胶原和PAF诱导的血小板聚集和TXB₂ 产生,并存在剂量依赖关系。在终浓度为5 μmol·L^-1 时,WR-2721 明显增加用ADP 、胶原和PAF 诱导的NO 的产生,表明活化血小板释放的NO 参与WR-2721 的抑制效应。结论 WR-2721 体外可有效地抑制生理性激活剂引起的血小板活化。除了细胞保护作用外,WR-2721 还可以用予治疗有关的疾病。

Effects of WR-2721, a cytoprotector of chemotherapy and radiation on functions of platelet in Chinese healthy volunteers

AIM: To explore in vitro the effects of WR-2721,a cytoprotector of chemotherapy and radiation,on platelet activation induced by physiologic agonists ADP,collagen and PAF.METHODS: Blood,obtained from Chinese healthy volunteers aged 20 -35 years,was treated with physiologic agonists at the given concentrations:ADp1 μmol·L^-1,collagen 2 mg·L^-1,and PAF0.1 mg·L^-1.Then WR-2721 was added to the experimental system at final concentrations range of 10^-7 -10^-5 mol·L^-1.The effect of WR-2721 on platelet aggregation induced by the agonists was studied.Thromboxane B₂(TXB₂)levels and nitric oxide(NO)production were determined.RESULTS: WR-2721 inhibited both platelet aggregation and TXB₂ production induced by ADP,collagen and PAF,in a dose-dependent manner.When WR-2721 was added at the final concentration of 5μmol·L^-1,it significantly increased ADP,collagen and PAF-induced NO production,which suggested that NO release by activated platelets was involved in the inhibitory effect of WR-2721.CONCLUSION: WR-2721 can effectively inhibit platelet activation induced in vitro by physiologic agonists.It may be not only a cytoprotectant,but also a therapeutic agent.