新型硫化氢释放型阿司匹林(ACS-14)对血小板聚集功能的影响

Effects of a novel hydrogen sulfide-releasing aspirin (ACS-14) on platelet aggregation

目的通过体外实验探索新型硫化氢(H2S)释放型阿司匹林(ACS-14)对血小板聚集功能的影响,并与其母体药物阿司匹林进行比较。方法采用光比浊法,检测阿司匹林、ACS-14和H2S释放基团(ACS-17)对腺苷二磷酸(ADP,2.5μmol·L-1)或凝血酶(0.1 U·mL-1)诱导的健康成人血小板聚集率的影响。结果不同浓度ACS-14(10、50、100、200μmol·L-1)预处理60 min后,ADP诱导的血小板聚集率均明显降低(P<0.05),分别为(63±5)%、(55±6)%、(43±3)%和(37±5)%;ACS-14(100μmol·L-1)预处理10、30、60和120 min后,ADP诱导的血小板聚集率也显著低于空白对照组(P<0.05),分别为(47±4)%、(42±4)%、(45±5)%和(40±5)%;ACS-14(≥100μmol·L-1,10 min、60 min和120 min)对ADP诱导的血小板聚集率显著低于等浓度的阿司匹林(P<0.05)。ACS-14(100μmol·L-1,60 min)可有效抑制凝血酶诱导的血小板聚集(P<0.05)。结论 ACS-14可呈浓度依赖性地抑制血小板聚集,起效迅速而持久,且这种抑制作用显著优于阿司匹林。

AIM To investigate the effects of a novel hydrogen sulfide （H2S） releasing aspirin （ACS- 14） on platelet aggregation and in comparison to its parent drug, aspirin. METHODS Human platelets were obtained from whole fresh blood drawn from healthy volunteers, then incubated with aspirin, ACS- 14 and ACS- 17 at different concentrations. Thereafter, platelet aggregations, induced by adenosine diphosphate （2.5 μmol L-1） were monitored by measuring the variation of light transmission. On the other hand, human platelets were incubated with aspirin, ACS- 14 and ACS- 17 （100 μmol L-1） for different durations, and then their aggregation was assayed. Platelet aggregations induced by thrombin （0.1 U mL-1） were also detected. RESULTS Pretreatment with ACS-14 （10, 50, 100 and 200 μmol L-1） for 60 min inhibited ADP-induced platelet aggregation by （63 ± 5） %, （55 ± 6） %, （43 ±3） %, （37 ± 5） %, respectively （P 〈 0.05 vs. the control group）. After incubated with ACS- 14 for 10 min, 30 min, 60 min and 120 min, percentage of platelet aggregation were （47 ± 4） %, （42 ±4） %, （45 ± 5） % and （40 ± 5） %, respectively （P 〈 0.05 vs. the control group） . Moreover, the anti-platelet property of ACS-14 （≥ 100 μmol L-1, incubated for 10 min, 60 min or 120 min） was more potent than aspirin at the same concentration （P 〈 0.05） . In addition, ACS-14 （100 μmol L-1, 60 min） significantly inhibited thrombin- induced platelet aggregation （P 〈 0.05）. CONCLUSION ACS- 14 inhibits platelets aggregation in a concentration- dependent manner, and its anti- platelet effect is more effective than aspirin.