萘哌地尔Ⅱ号衍生物YMⅡ对血小板聚集的影响及机制研究  

Effects of YMⅡ on platelet aggregation and its mechanisms

作　　者：覃明[1,2] 吴芹[1] 李向阳[3] 黄燮南[1] 

机构地区：[1]遵义医学院药理学教研室,贵州遵义563003 [2]遵义医学院免疫学教研室,贵州遵义563003 [3]商丘医学高等专科学校药理学教研室,河南商丘476100

出　　处：《遵义医学院学报》2009年第2期103-107,共5页Journal of Zunyi Medical University

摘　　要：目的观察萘哌地尔Ⅱ号衍生物YMⅡ对家兔血小板聚集的影响并对其进行机制研究,为该药的开发研究提供基础资料。方法①以比浊法观察YMⅡ对二磷酸腺苷(ADP),肾上腺素(Adr)或凝血酶(Thr)诱发的家兔血小板聚集的影响。②荧光法测定钙荧光指示剂Fura-2/AM负载的家兔血小板胞浆游离钙浓度([Ca2+]i),观察YMⅡ对ADP、Adr或Thr所致血小板([Ca2+]i)升高的影响。③用125I放射免疫法观察YMⅡ对ADP、Adr或Thr所致的血小板血栓烷A2(TXA2)的代谢产物血栓烷B(2TXB2)生成含量的影响。结果①YMⅡ高浓度(10-4mol·L-1)对ADP(1.5×10-5mol·L-1)、Adr(5.5×10-5mol·L-1)或Thr(0.6U/mL)诱发的家兔血小板聚集与溶媒组比较均有抑制作用;中浓度(10-5mol·L-1)对上述浓度的ADP和Adr诱发的家兔血小板聚集也有抑制作用,但对Thr(0.6U/mL)诱发的血小板聚集抑制作用不明显;低浓度(10-6mol·L-1)对ADP、Adr或Thr诱发的血小板聚集均没有抑制作用。②YMⅡ中浓度和高浓度能降低ADP和Adr所致的血小板([Ca2+]i)的升高;低浓度对其无抑制作用;该药对Thr,只有高浓度才有降低([Ca2+]i)作用。③上述三浓度的YMⅡ呈浓度依赖性地抑制ADP所致TXB2的升高作用;本品中浓度和高浓度对Adr所致的TXB2的升高也有抑制作用,低浓度则无抑制作用;上述高、中、低浓度的YMⅡ对Thr所致的TXB2的升高虽有一定的抑制作用,但不呈量效关系。结论YMⅡ对由ADP、Adr诱发的家兔血小板聚集有不同程度抑制作用,但对由Thr所诱发的血小板聚集却仅呈微弱的抑制,其抗血小板聚集的机制可能与其降低血小板([Ca2+]i)和减少TXA2生成等环节有关。Objective To supply a basic information for exploiting research of YM Ⅱ, we investigate the effects of YM Ⅱ （naftopidil＇s ramification） on platelet aggregation and its mechanisms in rabbits. Methods （1）To observe the effect of YM Ⅱ on rabbit＇s platelet aggregation induced by Adenosine diphosphate（ADP）,Adrenaline （Adr） and Thrombin（Thr） with turbidimetry.（2）Cytosolic free calcium concentration （[Ca^2＋]i） was measured in Fura-2/AM loaded platelet of rabbits by fluorometry to observe the effect of YM Ⅱ on the elevation of （[Ca^2＋]i） induced by ADP ,Adr or Thr. （3）Effect of YM Ⅱ on rabbit＇s platelet thromboxaneB,（TXB2） production was surveyed by radioimmunoassay（RIA） under the influence of ADP,Adr or Thr. Results （1）YM Ⅱ 10^-4mol·L^-1 had significant inhibitory effects on platelet aggregation of rabbit induced by ADP （1.5×10^- 5mol· L^-1）,Adr（5.5×10^-5mol· L^-1） or Thr（0.6U/mL）; YM Ⅱ 10^-5mol· L^-1 also had significant inhibitory effects on that induced by ADP and Adr, but no any influence on that induced by Thr; however, YM Ⅱ 10^-6mol ·L^-1 had no inhibitory effect on that induced by these aggregation cousing agents. （2）YM Ⅱ 10^-5 and 10^-4 mol ·L^-1 could inhibit significantly the elevations of platelet （[Ca^2＋]i） induced by ADP（1.5×10^-5mol·L^-1） or Adr （5.5×10^-5mol·L^-1） with a concentration-dependent manner , but YM Ⅱ 10^-6mol·L^-1 had no any effects on that induced by ADP and Adr. At the same time, YM Ⅱ inhibited that induced by Thr （0.6U/ml） only at 10.4 mol·L^-1 . （3）YM Ⅱ at the 10^-6 , 10^-5 ,10^-4 mol·L^-1 could inhibit the elevations of platelet TXB2 production induced by ADP（1.5× 10^-5mol· L^-1） with a concentration-dependent manner ; similarly, YM Ⅱ10^-5 and 10^-4 mol· L^-1 could also inhibit that induced by Adr （5.5×10^-5mol·L^-1）, but YM Ⅱ 10^-6mol·L^-1 had no effect on it. At the same time, YM Ⅱ 10^-6,10^-5 and 10^-4 mol·L^-1 had also inhibitory e

关 键 词：萘哌地尔Ⅱ号衍生物(YMⅡ) 血小板聚集 血小板内游离钙 血栓烷B2(TXB2) 

分 类 号：R973.2[医药卫生—药品]