体外细胞色素P450同工酶对银杏叶水提取物抗血小板聚集作用的影响

目的应用体外肝细胞模型研究中草药银杏叶提取物的代谢途径,即细胞色素P450酶(CYP450)药物代谢酶系对银杏叶拮抗血小板聚集效应的影响。方法制备人超低温冷冻肝细胞,通过与银杏叶提取物预孵育,评估肝脏CYP450药物代谢酶系(CYP1A2、CYP286、CYP2C19、CYP2E1、CYP3A4)对银杏叶水提取物拮抗血小板活化因子(PAF)激活的血小板聚集作用。富含血小板血清(PRP)和少含血小板血清(PPP)与不同质量浓度(25、50、100、200和1000μg·L~(-1))PAF孵育,建立PAF激活血小板聚集的体外模型。银杏叶水提物与人超低温冷冻复苏肝细胞预孵育后,与PRP和PAF培养,观察银杏叶水提物的体外效应(抗PFA血小板聚集激活作用)是否受人肝细胞代谢的影响。CYP450药物代谢酶的特定抑制物伊曲康唑(CYP3A4)、α-萘黄酮(CYP1A2)、奥芬那君(CYP286)、奥美拉唑(CYP2C19)、4-甲基吡唑(CYP2E1)与人肝细胞预孵育后、与银杏叶水提物和PRP和PAF孵育,评估银杏叶水提物的体外效应与何种CYP450药物代谢同工酶有关。结果PAF激活血小板聚集作用遵循米-曼氏动力学方程,其K_m为98μ·L~(-1)。银杏叶水提物抑制PAF的血小板聚集激活作用,其半数抑制剂量为33μg·L~(-1)。人肝细胞与银杏叶水提物预孵育后,其体外效应(抗PAF血小板聚集激活作用)增强30%,差异有统计学意义(P<0.05)。人肝细胞与细胞色素CYP450同工酶CYP286、CYP2C19、CYP2E1、CYP3A4抑制剂预孵育后,银杏叶水提物的体外效应不受影响。人肝细胞与CYP1A2抑制剂预孵育后,人肝细胞对银杏叶水提物体外效应的增强作用基本消失,差异有统计学意义(P<0.05)。结论银杏叶水提物在体外能抑制PAF的血小板聚集作用,人肝细胞能显著增强这一体外效应,CYP450药物代谢酶CYP1A2可能参与银杏叶的这一体外效应的代谢活化。     

银杏叶提取物影响急性脑梗死患者血小板聚集率的研究

目的 探讨银杏叶提取物对急性脑梗死患者血小板聚集率的影响.方法 选取急性脑梗死患者102例,按数字表法随机分为观察组与对照组,每组51例.对照组患者给予常规药物治疗,观察组组患者在对照组的基础上给予银杏叶提取物药物治疗.结果 两组患者治疗后ADP、AA和PAF诱导的血小板聚集率分别为（65.1±8.1）％、（71.2±3.6）％、（30.1±5.2）％、（39.8±5.8）％、（42.1±6.3）％、（49.6±6.1）％均显著低于治疗前的（78.1±9.2）％、（77.6±9.0）％、（57.1±8.2）％、（56.8±8.4）％、（62.4±8.6）％、（61.9±8.3）％,差异均有统计学意义（均P ＜0.05）.观察组患者治疗后ADP诱导的血小板聚集率为（65.1±8.1）％,显著低于对照组（t=5.732,P＜0.05）;观察组患者治疗后AA诱导的血小板聚集率为（30.1±5.2）％,显著低于对照组（t=6.897,P＜0.05）;观察组患者治疗后PAF诱导的血小板聚集率为（42.1±6.3）％,显著低于对照组（t=6.013,P＜0.05）.两组患者治疗后神经功能缺损评分分别为（5.98±1.09）分、（7.11±1.56）分,显著低于治疗前的（12.98 ±2.09）分、（11.75 ±1.74）分,差异均有统计学意义（均P ＜0.05）;观察组患者治疗后的评分为（5.98±1.09）分,显著低于对照组的（7.11±1.56）分（t=5.469,P＜0.05）.结论 银杏叶提取物可显著降低急性脑梗死患者的血小板聚集率,值得在临床中推广应用.     

银杏叶提取物在治疗慢性肺心病中的抗血小板作用

目的：观察银杏叶提取物（Ｅｇｂ７６１）在肺心病治疗中的作用,特别是抗血小板作用。方法：用流式细胞方法测定了２组慢性肺心病患者治疗前后的血小板表面ＣＤ４１和ＣＤ６２ｐ表达变化。结果：２组病人治疗后ＣＤ４１和ＣＤ６２ｐ表达均显著降低,Ｅｇｂ７６１治疗组较一般治疗更明显。结论：Ｅｇｂ７６１具有良好的改善血小板功能的作用,是一种有效的肺心病治疗辅助药。     

奥美拉唑和法莫替丁对冠心病患者氯吡格雷和阿司匹林抗血小板治疗的影响

目的研究奥美拉唑和法莫替丁对冠心病患者氯吡格雷和阿司匹林抗血小板治疗的影响。方法选择2011年6月至2013年1月在商丘市第一人民医院接受双重抗血小板治疗的186例冠心病患者。根据治疗方法不同分为对照组（66例）、奥美拉唑组（88例）和法莫替丁组（32例）。其中对照组患者使用阿司匹林肠溶片（0．1g／d）＋氯吡格雷片（75mg／d）;奥美拉唑组患者使用阿司匹林肠溶片（0．1g／d）＋氯吡格雷片（75mg／d）＋奥美拉唑（40mg／d,静脉滴注）;法莫替丁组患者使用阿司匹林肠溶片（0．1g／d）＋氯吡格雷片（75mg／d）＋法莫替丁（20mg,2次／d,口服）。检测指标：血小板聚集阈值,二磷酸腺背（ADP）和胶原蛋白诱导的血小板聚集率。结果对照组ADP-血小板聚集阈值为（3．5±1．0）μmol／L,法莫替丁组为（3．8±0．5）μmol／L,奥美拉唑组为（3．4±0．9）μmol／L,各组比较差异无统计学意义（P〉0．05）。对照组胶原蛋白-血小板聚集阈值为（1．93±0．25）mg／L,法莫替丁组为（1．99±0．03）mg／L,奥美拉唑组为（1．95±0．16）mg／L,各组比较差异无统计学意义（P〉0．05）。法莫替丁组和对照组在胶原蛋白0．5mg／L诱导的聚集率差异有统计学意义[（7．1±2．3）％比（9．4±6．6％）,P〈0．05],但法莫替丁组和对照组在胶原蛋白诱导的最大聚集率差异无统计学意义（P〈0．05）。血小板聚集率在对照组和奥美拉唑组间差异无统计学意义（P〉0．05）。结论冠心病患者在双重抗血小板治疗期间,联用奥美拉唑或法莫替丁并不影响氯吡格雷和阿司匹林的抗血小板作用。     

银杏叶提取物对血小板粘附及血栓形成的影响

目的 观察银杏叶提取物（GbE)对血小板粘附及血栓形成的影响。方法 血小板粘附性采用旋转玻球法;体内血栓形成采用动－静脉旁路血栓形成法;体外血栓形成采用Chandler法;采用剪尾法观察小鼠尾动脉出血时间。结果 GbE明显降低家兔血小板粘附率;减轻家兔动－静脉旁路形成血栓的重量;缩短大鼠体外形成血栓的长度,并减轻其干重;延长小鼠尾动脉出血时间。结论 GbE有一定的抗血小板粘附及血栓形成的作用。     

氯吡格雷与阿司匹林联用对急性轻度脑梗死患者抗血小板聚集及其活化作用的影响

目的:评价氯吡格雷与阿司匹林联用对急性轻度脑梗死患者抗血小板聚集及其活化作用的影响。方法:选取2015年9月—2016年10月间收治的急性轻度脑梗死患者86例,按随机数表法将其分为对照组和观察组,每组43例;对照组患者给予阿司匹林治疗,观察组患者在对照组基础上加用氯吡格雷治疗;比较两组患者治疗前后的NIHSS评分值和溶酶体颗粒膜糖蛋白(CD63)、α-颗粒膜糖蛋白(CD62P)测得值及血小板抑制率。结果:观察组患者用药后按NIHSS的评分值和CD63、CD62P测得值低于对照组(P<0.05);以及花生四烯酸(AA)、二磷酸腺苷(ADP)测得值高于对照组(P<0.05)。结论:氯吡格雷与阿司匹林联用可抑制急性轻度脑梗死患者血小板聚集和活化,改善患者神经功能。     

鬼针草提取物对血小板聚集功能的影响

鬼针草(Bidens bipinnata L)他小花鬼针草(Bidens parvieflora Willd)均属菊科鬼针草属植物,药用其全草。性味苦、平。具清热解毒,活血散瘀之功效。近年来临床观察和药理实验研究发现该药具有消炎、抗高血     

奥扎格雷抗血小板聚集作用的临床观察

目的比较奥扎格雷与阿司匹林对血小板聚集作用的影响,分析二者抵抗概率。方法脑梗死患者120例,随机分为奥扎格雷组与阿司匹林组(各60例),分别用二磷酸腺苷(ADP)、花生四烯酸(AA)诱导,进行血小板聚集试验,检测最大血小板聚集率(MAR)。各组患者均于入院当天、治疗第14天检测血小板聚集率。结果奥扎格雷组与阿司匹林组血小板聚集功能在同一诱导剂作用下,差异无统计学意义,都存在抵抗、半抵抗现象。结论奥扎格雷、阿司匹林对血小板聚集率影响的差异无统计学意义,均可作为抗血小板聚集药物,但也存在抵抗现象。奥扎格雷抗血小板聚集的长期临床效果、与其他抗血小板聚集药物联合应用能否解决抵抗问题,还需进一步的大规模临床实验研究。     

Effects of Berbamine on PAF Production in Human Neutrophils and on Platelet Aggregation

本实验研究了双苄基异喹啉类生物碱小檗胺（Ｂｅｒｂａｍｉｎｅ）对人中性粒细胞血小板激活因子（ＰＡＦ）的产生及ＰＡＦ引起的兔血小板聚集的影响，并与钙通道阻断剂维拉帕米进行比较。结果表明，小檗胺（５０μｍｏｌ／Ｌ，１００μｍｏｌ／Ｌ）和维拉帕米（１０μｍｏｌ／Ｌ，１００μｍｏｌ／Ｌ）预处理的人粒细胞，用Ａ－２３１８７攻击后，ＰＡＦ的产生明显降低。小檗胺和维拉帕米也能抑制ＰＡＦ（７０ｐｍｏｌ／Ｌ）引起的血小板聚集，其抑制作用呈剂量依赖性。本实验结果提示，小檗胺和维拉帕米对ＰＡＦ生成及血小板聚集的抑制作用可能与阻断钙离子内流有关。     

小檗胺对人中性粒细胞PAF生成和PAF诱导的兔血小板聚集的抑制作用

本实验研究了双苄基异喹啉类生物碱小檗胺（Berbamine)对人中性粒细胞血小板激活因子（PAF）的产生及PAF引起的兔血小板聚集的影响，并与钙通道阻断剂维拉帕米进行比较，结果表明，小檗胺（50umol/L,100umol/L)和维拉帕米（10umol/L,100umol/L）预处理的人粒细胞，用A－23187攻击后，PAF的产生明显降低，小檗胺和维拉帕米也能抑制PAF（70pmol/L)引起的血小板聚集，其抑制作用呈剂量依赖性，本实验结果提示，小檗胺和维拉帕米对PAF生成及血小板聚集的抑制作用可能与阻断钙离子内流有关。     

Platelet-released ADP stabilizes PAF-induced rabbit platelet aggregation by stabilizing intracellular calcium

ＰｌａｔｅｌｅｔｒｅｌｅａｓｅｄＡＤＰｓｔａｂｉｌｉｚｅｓＰＡＦｉｎｄｕｃｅｄｒａｂｂｉｔｐｌａｔｅｌｅｔａｇｇｒｅｇａｔｉｏｎｂｙｓｔａｂｉｌｉｚｉｎｇｉｎｔｒａｃｅｌｕｌａｒｃａｌｃｉｕｍ１ＹＩＦｕＸｉａｎ，ＧＵＯＺｈａｏＧｕｉ２（Ｌａｂ...     

Effect of active synthetic 2-substituted quinazolinones on anti-platelet aggregation and the inhibition of superoxide anion generation by neutrophils

Quinazolinones, 2-substituted and 3-substituted, mainly synthesized by microwave irradiation, were subjected to anti-platelet aggregation and inhibition of superoxide anion generation assays. Interestingly, 2-phenyl-4-quinazolinone (4) exhibited significant inhibitory activities toward platelet aggregation and neutrophil activation, and it might therefore serve as a prototype lead compound.     

Rutaecarpine衍生物的合成及体外抗血小板聚集活性

目的合成新的rutaecarpine衍生物并对其抗血小板聚集活性进行研究。方法先合成rutaecarpine,再进行N-取代反应,合成目标化合物,并测试所合成化合物的体外抗血小板聚集活性。结果与结论共合成6个未见文献报道的新化合物,它们的结构经1H-NMR和MS确证。初步体外药理实验结果显示:有4个新化合物对血小板聚集的抑制作用强于母体化合物rutaecarpine。     

花椒油素对兔血小板聚集的影响

花椒油素（ｘａｎｔｈｏｘｙｌｉｎ，ＸＴ）是从大戟科植物乌桕［Ｓａｐｉｕｍｓｅｂｉｆｅｒｕｍ（Ｌ）Ｒｏｘｂ］根皮中提取的化合物，分子式Ｃ１０Ｈ１２Ｏ４，相对分子质量：１９６２１。乌桕是传统的中药材，乌桕根皮有利水消积，杀虫、解毒之功效，主治水肿，臌胀...     

The effect of pre-induction clonidine on platelet aggregation during minor surgery

Objective: This paper reports the results of a prospective randomized double-blind trial on the effects of pre-operative clonidine on platelet aggregation. Methods: Thirty adult (ASA I–II) patients undergoing elective minor orthopaedic surgery were randomly allocated into three groups of ten patients each. In group I clonidine 2 μg · kg⁻¹, in group II clonidine 4 μg · kg⁻¹ and in group III saline placebo was administered intravenously before the induction of anaesthesia. Anaesthesia was induced with propofol and vecuronium and maintained with halothane-nitrous oxide. Platelet counts and aggregation tests were performed before (t₀) and 1 h (t₁) and 24 h (t₂₄) after administration of the study drug. Results: Changes in platelet counts among the groups and values over time were not significant. Both maximum rate and intensity of collagen-induced aggregation in both clonidine groups and maximum intensity of adenosine 5′-diphosphate (ADP)-induced aggregation in the high-dose clonidine group increased significantly at t₁. However, all these increases in aggregation were within the normal ranges. Conclusion: The effects of both low and high doses of clonidine on platelet aggregation appeared to be minor, and we did not observe any increases above the normal ranges. Received: 16 December 1997 / Accepted in revised form: 9 May 1998     

Triazolodiazepines are potent antagonists of platelet activating factor (PAF) in vitro and in vivo

Summary The triazolodiazepines brotizolam, triazolam and alprazolam inhibited PAF-induced human platelet aggregation in vitro (IC₅₀ = 0.54, 7.6 and 13.7 M, respectively) but showed only a weak or no effect against other aggregating agents (ADP, adrenaline, collagen, serotonin, arachidonic acid). In comparison, flunitrazepam and diazepam, two diazepines without the triazole ring, showed IC₅₀-values of 42 and 260 M, respectively. Flunitrazepam does not possess the specificity shown by the other compounds. Brotizolam and triazolam also inhibited PAF-induced human neutrophil aggregation in vitro, with IC₅₀-values 0.21 and 6.6 M, respectively.In anaesthetized guinea pigs, brotizolam (2.5 to 10 mg/kg p.o. or 0.1 to 0.5 mg/kg i.v.) or triazolam (20 to 100 mg/kg p.o.) inhibited dose-dependently the intrathoracic accumulation and aggregation of ¹¹¹Indium labelled platelets induced by an i. v. infusion of PAF (30 ng/kg × min).Brotizolam at doses of 1 to 10 mg/kg p. o. and 0.1 to 0.5 mg/kg i. v. inhibited dose-dependently the reduction in tidal volume (bronchoconstriction), the systemic hypotension and the lethal effect due to i. v. PAF in guinea pigs. Triazolam inhibited these effects of PAF at doses of 50 to 200 mg/kg p.o.PAF-induced systemic hypotension in rats can be reversed by cumulative i. v. doses (0.05 to 1.0 mg/kg) of brotizolam.In conclusion, these results show that triazolodiazepines, like brotizolam and triazolam, are potent inhibitors of PAF-induced effects in vitro and in vivo. Send offprint requests to J. Casals-Stenzel at the above address     

A novel anti-platelet aggregation tripeptide from Agkistrodon acutus venom: Isolation and characterization

AAP, a tripeptide that inhibited rabbit platelet aggregation, was isolated from Agkistrodon acutus venom by ion-exchange, gel filtration and reverse-phase chromatography. Amino acid sequences which determined mainly by amino acid analyses and NMR spectroscopy indicated it was a tripeptide including pyroglutamic acid, asparagine and tryptophane residues. The ESMS experiment assigned a molecular weight of 429 Da. AAP inhibited rabbit platelet aggregation induced by ADP, PAF-acether, collagen and thrombin, the IC₅₀s were 178 μM, 332 μM, 179 μM and 203 μM, respectively. AAP also inhibited thrombus formation in vivo thrombosis model and prevented the combination between fibrinogen and GP IIb/IIIa. Besides, AAP was not toxic after intravenous injection into mice at a higher dose. Those studies might be helpful to delineate unknown mechanisms involved in platelet aggregation and serve as a model for developing antithrombotic agents.