目的 比较两种前列腺素依前列醇钠、前列地尔在体外抑制二磷酸腺苷(adenosine diphosphate, ADP)诱导的血小板聚集的强弱。方法 SD大鼠腹腔静脉取血,制得血小板数400×109个/L的血小板混悬液。血小板混悬液中加入不同浓度的依前列醇钠和前列地尔(50、125、250、500、2500 ng/ml)在最佳ADP浓度和最佳孵育时间,分别测定5 min内最大聚集率,各浓度检测4次取平均值,从而得到依前列醇钠、前列地尔量效关系并进行对比。结果 ADP最佳诱导浓度为20 μM,最佳孵育时间为5 min,随着依前列醇钠、前列地尔浓度的增加,血小板聚集率依次降低。依前列醇钠5个浓度血小板抑制率依次为19.61%、48.13%、88.25%、93.71%和100.00%,前列地尔5个浓度血小板抑制率依次为5.20%、11.70%、23.16%、28.10%和65.09%。结论 依前列醇钠、前列地尔均具有血小板聚集抑制作用,并呈浓度依赖性,且依前列醇钠的血小板抑制作用远远强于前列地尔。
Abstract
ObjectiveTo investigate the inhibitory effects of two types of prostaglandins(epoprostenol sodium and prostaglandin E1) on adenosine diphosphate (ADP)-induced platelet aggregation in vitro.Methods Platelet suspension was incubated with epoprostenol sodium and prostaglandin E1 respectively at different concentrations(0, 50, 125, 500 and 2500 ng/ml)before the maximal extent of platelet aggregation was determined at the best ADP concentration and the best incubation time.Results At 20 μM ADP and after incubation of 5 min, the platelet aggregation of both types of prostaglandins induced by ADP was reduced accordingly with the increase of the concentrations of epoprostenol sodium and prostaglandin E1. The inhibitory rate of platelet aggregation induced by epoprostenol sodium was 19.61%, 48.13%, 88.25%, 93.71%, and 100% respectively,compared with 5.20%, 11.70%, 23.16%, 28.10% and 65.09% respectively for prostaglandin E1.Conclusions Epoprostenol sodium and prostaglandin E1 can inhibit ADP-induced platelet aggregation in a concentration-dependent manner in vitro, and the former is more effective.
关键词
依前列醇钠 /
前列地尔 /
二磷酸腺苷 /
血小板聚集率
Key words
epoprostenol sodium /
prostaglandin E1 /
adenosine diphosphate /
platelet aggregation
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Weiss H J, Turitto V T. Prostacyclin (Prostaglandin I2, PGI2) inhibits plat-elet adhesion and thrombus formation on subendothelium[J], Blood, 1979, 53(2): 244-250.
[2] O’Connell C, Amar D, Boucly A, et al. Comparative safety and tolerability of prostacyclins in pulmonary hypertension[J], Drug Saf, 2016, 39(4): 287-294.
[3] Akagi S, Nakamura K, Matsubara H, et al. Epoprostenol therapy for pulm-onary arterial hypertension[J], Acta Med Okayama, 2015, 69(3): 129-136.
[4] Chin K M, Badesch D B, Robbins I M, et al. Two formulations of epoprostenol sodium in the trea tment of pulmonary arterial hypertension: PITOME-1 (epoprostenol for injection in pulmonary arterial hypertension), aphase Ⅳ, open-label, randomized study[J]. Am Heart J, 2014, 167(2): 218-225.
[5] 王 琳.前列地尔联合甲钴胺治疗糖尿病视网膜病变临床疗效观察[J].临床合理用药,2018, 11(3): 58-59.
[6] 周俊江.探讨前列地尔治疗突发性耳聋的临床应用价值[J]. 江西医药, 2013, 48(12): 1261-1262.
[7] 樊华英,李慧娟,韩俊霞. 前列地尔联合厄贝沙坦治疗对老年糖尿病肾病患者蛋白尿、hs-CRP的效果分析[J]. 中国现代药物应用,2018,12(22): 126-127.
[8] 江思德,肖 静,邹耀兵,等. 前列地尔注射液治疗急性脑梗死44例临床疗效研究[J]. 中国药业, 2015, 24(24):31-32.
[9] 李珊珊.硫辛酸与前列地尔联合治疗糖尿病早期微血管病变的临床观察[J]. 药物研究, 2016, (7):78.
[10] 傅桥菲, 陈春林. 前列地尔治疗高血压视网膜病变的临床研究[J].江西医药, 2018, 53(11): 1321-1323.
[11] 方淑贤,郑 恒,刘 东,等. 穿心莲内酯对二磷酸腺苷诱导血小板聚集的拮抗作用[J]. 医药导报, 2004 23(11):805-806.
[12] 但 刚, 罗鸿雁, 江忠勇,等. 不同血小板浓度对血小板聚集率的影响探讨[J]. 西南国防医药, 2016, 26(8):832-834.
[13] 林兆瑛.血小板聚集素(TXA_2)和前列腺环素(PGI_2)[J]. 四川生理科学动态, 1983 (1):9-15.
[14] Fred V, Victor A, Skrinska, et al. Stability of prostacyclin in human and rabbit whole blood and plasa[J], Thromab Res, 1986,43:379-387.
[15] 内阁莱什.R.帕莱普. 新颖的依前列醇制剂及其制备方法[P].中国专利,公开号:CN 101410119.
[16] Madelene Lindkvist,Ulrika Fernberg,Liza U. Individual variations in platelet reactivity towards ADP, epinephrine, collagen and nitric oxide, and the association to arterial function in young, healthy adults[J]. Thromb Res, 2019, 174: 5-12.
[17] 翟 婷,华声瑜. 血小板ADP受体及其拮抗剂的研究进展[J]. 天津中医药, 2017, 34(4):280-284.
PDF(696 KB)
