dl—四氢巴汀对实验性脑血栓形成及体外血小板聚集的抑制作用

目的：观察ｄｌ－四氢巴马汀对大鼠实验性脑血栓形成的影响。并观察体外ｄｌ－ＴＨＰ对二磷酸腺苷，花生四烯酸和胶原诱导的兔上板聚集的影响。方法：采用经大鼠颈动脉顺行注射复合血栓诱导剂（二磷酸腺苷、凝血酶和肾腺素）造成的脑血栓模型。结果：ｄｌ－ＴＨＰ（１５、７．５ｍｇ．ｋｇ＾－１）ｉｖ对大鼠实验性脑血栓形成有明显的抑制作用。ｄｌ－ＴＨＰ对二磷腺苷、花生四烯酸和胶原诱导的兔血小板聚集均有抑制作用，并呈剂量依     

抗血小板膜糖蛋白Ib凝血酶受体单抗的制备及功能研究

目的：制备抗人血小板膜糖蛋白Ib(GPIb)单克隆抗体（单抗）并研究其功能，方法：杂交瘤技术制备单抗，HLISA法筛选与Western blot鉴定单抗识别的抗原，比浊法检测该单抗对血小板聚集的抑制作用。结果：（1）获得一株新的抗人血小板膜糖蛋白单抗SZ16。（2）在非还原状态下，SZ16识别分子量165000的抗原，表明SZ16抗原为GPIb.(3)该单抗为IgG1亚类。（4）FCM检测表明，,SZ16与正常人及血小板无力症（GT）患者血小板结合率很高，用凝血酶处理血小板后，几乎完全阻断SZ16与血小板的结合。（5）该单抗抑制低浓度凝血酶引起的血小板聚集，对ADP，瑞斯托霉素和花生四烯酸引起的血小板聚集无抑制作用。结论：SZ16为一株新的抗GPIb凝血酶受体的单抗。     

dl-四氢巴马汀对实验性脑血栓形成及体外血小板聚集的抑制作用

目的：观察ｄｌ－四氢巴马汀（ｄｌ－ＴＨＰ）对大鼠实验性脑血栓形成的影响。并观察体外ｄｌ－ＴＨＰ对二磷酸腺苷、花生四烯酸和胶原诱导的兔血小板聚集的影响。方法：采用经大鼠颈动脉顺行注射复合血栓诱导剂（二磷酸腺苷、凝血酶和肾上腺素）造成的脑血栓模型。结果：ｄｌ－ＴＨＰ（１５、７．５ｍｇ·ｋｇ－１）ｉｖ对大鼠实验性脑血栓形成有明显的抑制作用。ｄｌ－ＴＨＰ对二磷酸腺苷、花生四烯酸和胶原诱导的兔血小板聚集均有抑制作用，并呈剂量依赖关系。结论：其作用可能是通过拮抗钙离子的作用而产生。     

白唇竹叶青蛇毒5′-核苷酸酶对血小板聚集的影响及其机制研究

目的研究白唇竹叶青蛇毒5′-核苷酸酶对血小板聚集的影响,探讨其作用机制。方法采用比浊法测定白唇竹叶青蛇毒5′-核甘酸酶对二磷酸腺苷(ADP)、花生四烯酸(AA)、血小板活化因子(PAF)诱导血小板聚集的影响。结果白唇竹叶青蛇毒5′-核甘酸酶能抑制ADP、AA、PAF诱导的血小板聚集,且其抑制率与剂量增加成正比;抑制血小板聚集作用与ADP的水解和腺苷的积累有关。结论白唇竹叶青蛇毒5′-核甘酸酶能抑制血小板聚集,抑制作用主要通过水解ADP和积累腺苷,可能与阻断TXA2的生成有关。     

蛇毒抗补体蛋白atrase B抑制补体活化引起的血小板聚集

目的观察眼镜蛇毒抗补体蛋白atrase B抑制补体活化引起的血小板聚集。方法采用眼镜蛇毒因子激活补体诱导血小板聚集,观察atrase B对补体活化引起人凝胶过滤血小板聚集的影响,并采用流式细胞仪测定血小板膜P-选择素和GPⅡb/Ⅲa表达情况。结果Atrase B能抑制补体激活引起的血小板聚集和P-选择素、GPⅡb/Ⅲa在血小板膜上的表达。结论眼镜蛇毒抗补体蛋白atrase B能有效抑制补体激活引起的血小板活化、聚集。     

二甲基亚砜对人体血小板聚集的作用

本文研究万能溶媒二甲基亚砜对内源性介质二磷酸腺苷、肾上腺素、花生四烯酸、胶原和血小板活化因子诱致的人体血小板聚集作用的影响。方法:聚集试验的血样采用枸橼酸盐-富含血小板血浆(PRP)(血液与3.8%枸橼酸钠溶液比为9∶1)。聚集剂浓度为二磷酸腺苷4μM,肾上腺素1μM,花生四烯酸0.5mM,胶原10μg/ml,血小板活化因子1μM,聚集试验按Born&Cross方法进行。由光密度变化和在0.25、0.5、1、2、3和5%DMSO     

融斑通脉颗粒对家兔血小板聚集的影响

目的观察融斑通脉颗粒对家兔血小板聚集的影响。方法使用二磷酸腺苷(ADP),花生四烯酸和胶原等促凝剂促进血小板凝聚,采用Born氏比浊法,观察融斑通脉颗粒对家兔血小板聚集的影响,并与对照组及阿司匹林组比较。结果家兔连续7 d灌胃给药,融斑通脉颗粒明显降低胶原,ADP诱导的家兔血小板聚集率(P<0.05~0.01),对花生四烯酸诱导的家兔血小板聚集率有降低趋势。结论融斑通脉颗粒具有抑制血小板聚集的作用,为其临床治疗缺血性心脏病提供了实验依据。     

金环蛇毒组份Ⅺ兔血小板聚集功能的影响

本文采用CM-Sephadex C-50柱层析分离金环蛇原毒,得16个峰,其中组份Ⅰ有促进兔血小板聚集的作用,其聚集曲线呈两个聚集波,原毒及组份Ⅶ～ⅩⅣ对ADP诱导的血小板聚集有抑制作用,其中组份Ⅺ经DEAE-Sephadex A-50柱层析纯化,经聚丙烯酰胺圆盘电泳鉴定为单一区带,组份Ⅺ可使小鸡颈二腹肌产生挛缩,且抑制离体蛙心收缩,该组份没有ADP酶及5′-核苷酸酶活力,但有磷脂酶A_2活力,原毒及组份Ⅺ的LD_(50)(小鼠ip)分别为1.5±s 0.2及8.0±s 1.3 mg·kg~(-1)(95％可信限),组份Ⅺ不引起富血小板血浆中乳酸脱氢酶含量升高,对ADP,花生四烯酸,A23187及凝血酶诱导的血小板聚集均有抑制作用,其IC_(50)分别为:68.8,10.0,10.1,6.3μg·ml~(-1),但对血小板5羟色胺的释放无明显影响,其作用机理需进一步研究。     

酸枣仁皂苷A的抗血小板聚集活性研究

目的 研究酸枣仁皂苷A的抗血小板聚集活性。方法 采用兔体外血小板聚集实验方法,结合酶联免疫吸附法测定血清血小板活化因子（platelet activating factors,PAF）、P-选择素和血小板因子-4（platelet factor-4,PF-4）的含量,探讨不同浓度的酸枣仁皂苷A对二磷酸腺苷（adenosine diphosphate,ADP）、花生四烯酸（arachidonic acid,AA）和PF-4诱导血小板聚集的抑制活性。结果 酸枣仁皂苷A能有效抑制AA、ADP和PF-4诱导的血小板聚集,能显著降低PAF、P-选择素和PF-4的含量。结论 酸枣仁皂苷A具有明显的抗血小板聚集活性。     

香草酸抗血小板聚集作用的体内外研究

目的香草酸是一种酚酸类化合物,具有抗氧化、抗炎等药理作用,其抗血栓作用尚未有报道。本实验室前期通过筛选发现香草酸具有良好的抗血小板聚集作用,因此本研究通过体内外实验对香草酸抗血小板聚集的作用进行系统评价。方法采用花生四烯酸(arachidonic acid,AA)、二磷酸腺苷(adenosine diphosphate,ADP)、凝血酶(thrombin,THR)诱导体内外血小板聚集模型,结合凝血四项检测评价香草酸抗血小板聚集及抗血栓的作用。结果体外实验中,香草酸对ADP和AA诱导的血小板聚集具有显著抑制作用,并剂量依赖性抑制ADP诱导的血小板聚集;体内试验中,香草酸(10、30和100 mg/kg)能够剂量依赖性抑制ADP和AA诱导的血小板聚集;同时,香草酸(100 mg/kg)能显著降低纤维蛋白原、增加凝血酶原时间,对活化部分凝血活酶时间和血浆凝血酶时间无明显影响。结论本研究首次发现香草酸对ADP和AA诱导的血小板聚集具有抑制作用,为研发具有自主知识产权的抗血小板聚集药物提供了实验依据。     

尖吻蝮蛇毒小分子多肽的分离及抗血小板聚集作用

目的从尖吻蝮蛇毒中分离纯化一种抗血小板聚集小分子多肽,研究其理化性质以及对ADP、胶原、凝血酶诱导的血小板聚集反应的影响。方法经SephadexG-75凝胶过滤,超滤,DEAE-SepharoseCL-6B离子交换层析法分离纯化蛇毒组分,采用高效液相鉴定纯度,用SDS-凝胶电泳(SDS-PAGE)测定其分子量,用比浊法测定其抗血小板聚集活性。结果从尖吻蝮蛇毒中分离相对分子质量约为7862u等电点为4.29的组分,该组分能抑制由ADP、胶原、凝血酶诱导的血小板聚集并成剂量依赖性。结论此法成功地从尖吻蝮蛇毒中纯化出抗血小板聚集组分。该组分与去整合素比较相似,可能属于去整合素家族。     

Dicentrine, a novel antiplatelet agent inhibiting thromboxane formation and increasing the cyclic AMP level of rabbit platelets.

Dicentrine is an antiplatelet agent isolated from the Chinese herb Lindera megaphylla. We examined the in vitro effects of dicentrine on various aspects of platelet reactivity. Dicentrine inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA), collagen, ADP, platelet-activating factor (PAF), thrombin and U46619. Dicentrine also inhibited the thromboxane B2 formation caused by AA, collagen and thrombin in washed intact platelets or that induced by AA in lysed platelet homogenate, while prostaglandin D2 formation caused by AA was not increased. The generation of inositol monophosphates (in the presence of indomethacin) caused by thrombin, collagen and PAF was not suppressed significantly, nor did dicentrine suppress fibrinogen-induced aggregation of elastase-treated platelets. Dicentrine inhibited the intracellular Ca2+ increase in quin-2/AM-loaded platelets caused by thrombin, PAF, collagen and AA. The cyclic AMP level was elevated by dicentrine in a concentration-dependent manner. These data indicate that the inhibitory effect of dicentrine on platelet aggregation and ATP release was due to the inhibition of thromboxane formation and the elevation of the level of cyclic AMP.     

Effect of cefaclor on guinea pig platelet aggregation in vitro

Effects of cefaclor (3-chloro-7-D-(2-phenyl-glycinamido)-3-cephem-4-carboxylic acid) on PAF, ADP, collagen, endotoxin, and thrombin-induced platelet aggregation were examined in vitro with the use of guinea pig platelet-rich plasma and washed platelets. PAF, even at concentrations lower than its minimum effective concentration, enhanced ADP- or endotoxin-induced platelet aggregation and prolonged the time to attain the maximum aggregation. PAF also enhanced collagen-induced platelet aggregation and shortened the lag time. Cefaclor (CCL) inhibited the PAF, ADP or thrombin induced platelet aggregation and shortened their maximum aggregation times at higher concentrations such as 300 micrograms/ml or more. CCL also inhibited the collagen-induced platelet aggregation and prolonged the lag time, but showed no effect on endotoxin-induced platelet aggregation. The effect of CCL was almost the same as that of latamoxef (LMOX). CCL and LMOX, however, showed no effect on cellular Ca2+ increase produced by PAF, ADP, or thrombin, suggesting that the inhibitory effect of CCL and LMOX on platelet aggregation is caused by the inhibition of fibrinogen binding to the glycoprotein IIb/IIIa complex.     

烙铁头蛇毒血小板聚集素对血小板聚集和抑制剂关系的研究

研究山莨菪碱(654-2)、阿斯匹林(ASA)、前列环素(PGI_2)样物质对二磷酸腺苷(ADP)、花生四烯酸(AA)以及烙铁头蛇毒血小板聚集素(TMVA)诱导的阻抗法全血血小板聚集(简称全血聚集)的影响。结果表明:ADP.AA.TMVA诱导的全血聚集随剂量增加而增强.阻抗技术对于估价生理条件下的血小板功能较为敏感。654-2促进ADP诱导的全血聚集.而ASA和PGI_2样物质对ADP和AA诱导的聚集均有抑制作用.但不能防止TMVA诱导的聚集。提示TMVA可能通过第3途径(类似于血小板活化因子.PAF)诱导血小板聚集.经ADP和AA作用过的血小板对TMVA的活化仍有反应,其机理值得研究。     

乙酰丹酚酸A对血小板功能的影响

乙酰丹酚酸以A(ASAA)是丹参有效成分衍生物。体外实验表明,ASAA对ADP、胶原、AA和凝血酶诱导的大鼠和兔血小板聚集有明显抑制作用。在半体内实验中,ASAA对多种诱导剂所致血小板聚集也有显著抑制作用,且持续时间达2h以上。此外,在抑制血小板聚集的同时,ASAA对胶原诱导的血小板5-HT释放也有显著抑制作用。上述结果提示,ASAA可能是一作用广泛的血小板功能抑制剂。     

Oncocalyxone A inhibits human platelet aggregation by increasing cGMP and by binding to GP Ibalpha glycoprotein

BACKGROUND AND PURPOSE: Oncocalyxone A (OncoA) has a concentration-dependent anti-platelet activity. The present study aimed to further understand the mechanisms related to this effect. EXPERIMENTAL APPROACH: Human platelet aggregation was measured by means of a turbidimetric method. OncoA (32-256 microM) was tested against several platelet-aggregating agents, such as adenosine diphosphate (ADP), collagen, arachidonic acid (AA), ristocetin and thrombin. KEY RESULTS: OncoA completely inhibited platelet aggregation with a calculated mean inhibitory concentration (IC50-microM) of 122 for ADP, 161 for collagen, 159 for AA, 169 for ristocetin and 85 for thrombin. The anti-aggregatory activity of OncoA was not inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). OncoA, at a concentration that caused no significant anti-aggregatory activity, potentiated sodium nitroprusside (SNP) anti-aggregatory activity (18.8+/-2.9%-SNP vs 85.0+/-8.2%-SNP+OncoA). The levels of nitric oxide (NO) or cAMP were not altered by OncoA while cGMP levels were increased more than 10-fold by OncoA in resting or ADP-activated platelets. Flow cytometry revealed that OncoA does not interact with receptors for fibrinogen, collagen or P-selectin. Nevertheless, OncoA decreased the binding of antibodies to GP Ibalpha, a glycoprotein that is related both to von Willebrand factor and to thrombin-induced platelet aggregation. CONCLUSION AND IMPLICATIONS: OncoA showed anti-aggregatory activity in platelets that was associated with increased cGMP levels, not dependent on NO and with blocking GP Ibalpha glycoprotein. This new mechanism has the prospect of leading to new anti-thrombotic drugs.