噻氯匹定对脑梗死病人血小板聚集的影响

目的：观察噻氯匹定对急性脑梗死的治疗效果及其对血小板聚集的影响。方法：脑梗死病人１１９例，随机分成噻氯匹定组和基础治疗（右旋糖酐＿４０，三磷腺苷二钠，辅酶Ａ，胞磷胆碱等）对照组，观察疗效，并于治疗前、治疗７ｄ和１６ｄ后检测血小板聚集率。结果：噻氯匹定组有效率达９６％；明显降低血小板聚集率，较对照组有显著性差异。结论：噻氯匹定可用于脑梗死急性期的治疗，抑制血小板聚集是其重要的治疗机制。     

国产盐酸噻氯匹啶片抗血小板聚集的临床验证

系前瞻性研究，观察盐酸噻氯匹啶抗血小板聚集作用。149例用药前血小板聚集功能≥50％者入选，其中55例随机分组与肠溶阿斯匹林对照。试验组（T组）眼盐酸噻氯匹啶250mg／日，对照组（C组）服肠溶阿斯匹林75mg／日，均为4周。眼药后2周末、4周末测定血小板聚集功能（ADP诱导，0．2μmol／L）证实盐酸噻氯匹啶抗血小板聚集功能确切，显效率61．1％，总有效率96．8％。肠溶阿斯匹林亦能降低血小板聚集功能，显效率14．8％，总有效率61．1％。盐酸噻氯匹啶不良反应与肠溶阿斯匹林相近，不良反应发生率10．5％。     

常用抗血小板制剂疗效及性别差异的比较

目的：观察噻氯匹定,阿斯斯匹林（ＡＳＡ）抑制血小板聚集功能在男女患者疗效的差异性。方法：１２４例用药前血小板聚集功能≥５０％者入选,男女患者各６２例,再随机分成噻氯匹定Ｔ组（男Ｔ１、女Ｔ２）和阿斯匹林Ｃ组（男Ｃ１、女Ｃ２）,Ｔ组口服噻氯匹定２５０ｍｇ／ｄ,Ｃ组口服ＡＳＡ ７５ ｍｇ／ｄ均为４周,服药后２周末、４周末测定血小板聚集功能（ＡＤＰ）诱导０．２μｍｏｌ／Ｌ）．结论：证实噻氯匹定抗血小板聚集率优于ＡＳＡ。噻氯匹定显效率男６８％、女６２．８ ％,总有效率为男９６．８％,女９５．７％。且证明男女疗效无明显差异．而ＡＳＡ显效率男１８％、女１３％,总有效率男７２．３％女１５％,男女疗效有显著不同。     

噻氯匹定对冠心病病人血小板聚集的抑制作用

例，噻氯匹定组用噻氯匹定２５０ｍｇ，ｐｏ，ｂｉｄ，阿司匹林组用阿司匹林１５０ｍｇ，ｐｏ，ｑｄ，共４ｗｋ。结果：２个治疗组用药后血小板聚集率均有下降（Ｐ＜０．０５），而对照组无变化。在服药后１ｗｋ内起效，１～４ｗｋ作用平稳。２组血小板聚集率下降，噻氯匹定大于阿司匹林（Ｐ＜０．０５）。结论：噻氯匹定对冠心病心绞痛病人血小板聚集的抑制作用效果肯定。     

噻氯匹啶对血小板聚集功能的抑制作用研究

观察了噻氯匹啶（TP）对血小板聚集的影响，结果表明在体外可显著抑制ADP、花生四烯酸和凝血酶诱导的大鼠或人血小板聚集，其IC50分别为1．035、1.047和0．092mmol／L，在体内连到给药（TP：50－200mg／kg·d－1）7d可抑制ADP和凝血酶诱导的大鼠血小板聚单，提示TP是一个较强的血小板聚集抑制剂。     

噻氯匹定对冠心病病人血小板聚集的抑制作用

目的：观察噻氯匹定对冠心病心绞痛病人血小板聚集的抑制作用，方法：１１４例冠心病心能病人，男性７９例，女性３５例，年龄４９±ｓ１１ａ，随机分为噻氯匹定组，阿司匹林组及空白对照各组３８例，噻氯匹定组用噻氯匹定２５０ｍｇ，ｐｏ，ｂｉｄ，阿司匹林组用阿司匹林１５０ｍｇ，ｐｏ，ｑｄ，共４ｗｋ，结果：２个治疗组用药后血小板聚集率均有下降（Ｐ〈０．０５），而对照组无变化，在服药后１ｗｋ内起效，１～４ｗｋ作用平稳     

噻氯匹啶的抗血小板机理和临床应用

噻氯匹啶（Ticlopidne）商品名力抗性，是一种抗血小板新药，1974年被发现其有抗血小板聚集活性，1983年以后在欧洲、日本和拉美许多国家广泛应用，1989年我国批准引进该药．噻氯匹啶化学名5－（O－chlorobenzyl）－4，5，6，7－tetrahydrothieno（3，2—C）PyridneHCI．药理作用：噻氯匹啶能抑制血小板的聚集和释放机能，延长出血时间，仅在体内有效．血小板膜上有纤维蛋白原受体，可被多个因子激活，使纤维蛋白原在血小板间形成间桥而聚集（见附图）．血小板的激活因子有（1）组织损伤处的胶原．（2）凝血酶，（3）ADP（＝磷酸腺苷）…     

榄香烯抑制表皮生长因子诱导的晶状体上皮细胞增殖的信号转导机制

目的：研究榄香烯（elenene，Ele）抑制重组人表皮生长因子（recombinant human epidermal growth factor，rhEGF）诱导的晶状体上皮细胞（lens epithelium cell，LEC）增殖时对细胞内钙（Ca^2＋）、环磷酸腺苷（cyclic adenosine monophosphate，cAMP）、环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）的影响，探讨其抑制增殖的细胞信号转导机制。方法：采用rhEGF诱导LEC增殖后，用荧光分光光度法检测LEC内钙离子浓度（[Ca^2＋]i）、放射免疫分析法检测LEC内cAMP和cGMP含量，探讨Ele的影响。结果：（1）Ele组LEC内[Ca^2＋]i；比增殖组显著增高（P〈0．01）；（2）增殖组LEC内cAMP浓度比对照组明显下降、cGMP浓度比对照组明显升高（P〈0．01）；（3）Ele组LEC内cAMP浓度比增殖组显著升高、cGMP浓度比增殖组显著降低（P〈0．01）。结论：Ele抑制LEC增殖的作用是通过细胞内[Ca^2＋]i、cAMP和cGMP信号系统及多条信号转导途径的相互作用实现的，这可能是Ele抑制LEC增殖、防治后发性白内障的细胞和分子生物学机制。     

噻氯匹定和阿司匹林降低血液粘度和抗血小板作用的比较

目的：比较噻氯匹定和阿司匹林对冠心病病人血液粘度、血小板聚集率和血凝系统的作用。方法：噻氯匹定（０ ．２５ ｇ , ｐｏ,ｂｉｄ） 治疗４４ 例病人。阿司匹林（５０ ｍｇ , ｐｏ,ｂｉｄ） 治疗４５ 例病人。均连续用药４ ｗｋ 。结果：２ 组均有降低全血粘度、血浆粘度、血小板聚集率、延长活化的部分凝血活酶和凝血酶原时间等作用。组间比较：Ｐ＞ ０ ．０５ 。结论：２ 药均有降低血液粘度、血小板聚集率和抑制凝血功能的作用。     

噻氯匹定对血小板血栓烷B_2生成的影响

口服噻氯匹定(ticlopidine)能抑制胶原诱导的血小板血栓烷B_2(TXB_2)生成。大剂量(500mg/d)可使TXB_2生成很快降低,停药1wk后恢复正常。给小剂量(250mg/d)时TXB_2的减少出现较晚,恢复亦快。噻氯匹定对ADP诱导的血小板TXB_2生成也有显著抑制作用。噻氯匹定的抗血小板作用至少有部分与抑制花生四烯酸的代谢有关。     

甲基莲心碱对兔血小板聚集功能的影响

用比浊法和放射免疫分析技术研究甲基莲心碱(Nef)抗血小板聚集作用及其对TXA₂/PGI₂与cAMP/cGMP浓度的影响。结果显示,Nef在体外明显抑制ADP,胶原,AA及PAF诱导的家兔血小板聚集,IC₅₀分别为16,22,193及103μmol·L^-1;Nef明显抑制AA诱导的血小板TXA₂的生成和释放,对动脉环PGI₂的生成有促进作用;Nef剂量依赖性地升高血小板cAMP浓度,对cGMP无明显影响。结果提示Nef抗血小板聚集作用的机理与抑制TXA₂生成,增加血管PGI₂及血小板cAMP含量有关。     

Effect of heparin and dihydroergotamine on platelet adenosine-3',5'-cyclic monophosphate

Human platelet adenosine-3',5'-cyclic monophosphate (cAMP) levels were determined in platelet rich plasma (PRP) and in washed platelets by a modification of the protein binding assay; the validation of the method is described. Dihydroergotamine (DHE) inhibited epinephrine induced platelet aggregation (ID50 = 2.5 X 10(-7) mol/l), and increased cAMP levels in platelets by an alpha-adrenergic receptor blocking effect, since phentolamine but not propranolol, behaved similarly. The DHE induced cAMP accumulation was correlated to the inhibitory effect on aggregation and showed a characteristic alpha-adrenergic receptor pattern in the presence of alprostadil (PGE1) and epinephrine but not collagen or adenosine diphosphate (ADP). Thrombin induced aggregation was similarly affected by DHE but with 100 times higher concentration. Heparin was found to increase slightly ADP and epinephrine induced aggregation and to decrease cAMP. Also, heparin was found to inhibit thrombin induced platelet aggregation. In washed platelets, the inhibitory effect of thrombin on PGE1 induced cAMP accumulation was counteracted by heparin. This indicates that the binding site of thrombin on platelets is important in the control of adenyl cyclase. Evidence is presented that some of the beneficial synergistic effect of DHE and heparin may consist in the ability of those compounds to produce opposite effects on cAMP system in platelets.     

二磷酸腺苷诱导的血小板聚集率测定方法研究

目的：研究二磷酸腺苷（ADP）诱导的血小板聚集率的测定方法。方法：收集30例急性冠脉综合征（ACS）患者的血样,选择5,10,20μmol·L＾-1不同浓度的ADP测定血小板1,3,5min的聚集率和最大聚集率。结果：5μmol·L^-1ADP组不同时间点的血小板聚集率与10,20μmol·L^-1ADP组差异显著（P〈0．01）,10μmol·L^-1ADP组不同时间点的血小板聚集率与20μmol·L。ADP组差异无统计学意义。研究发现血小板聚集率有直方双曲线和波形图两组有代表性的图形。结论：对于普利生公司的LBY—NJ4四通道血小板聚集仪,10μmol·L^-1为最适ADP诱导剂浓度。初步推断患者的血小板聚集率的图形为直方双曲线,可能对氯吡格雷的反应较高,氯吡格雷能起到较好的抗血小板作用。     

三乙酰莽草酸对血小板聚集的抑制作用

目的：研究三乙酰莽草酸（TSA）对血小板聚集功能的抑制作用及其作用机理。方法：用比浊法测定血小板聚集功能,分光光度法测定MDA的含量,放免法测定TXB₂,6-酮-PGF_1α,cAMP和cGMP的含量。结果：TSA 12.5,25,50,100和200 mg.kg^-1 ig明显抑制ADP和胶原诱导的大鼠血小板聚集;TSA 12.5,50和200　mg.kg^-1 ig显著增加大鼠血小板内cAMP水平,但不影响cGMP水平。TSA 200 mg.kg^-1对AA诱导的血小板中MDA的生成,ADP诱导的血小板中TXB2和腹主动脉壁6-酮-PGF_1α的生成有轻度抑制作用。结论：TSA抑制血小板聚集作用部分与血小板内cAMP水平升高有关。     

Ginkgolide C inhibits platelet aggregation in cAMP- and cGMP-dependent manner by activating MMP-9

In this report, we investigated the effect of ginkgolide C (GC) from Ginkgo biloba leaves in collagen (10 mug/ml)-stimulated platelet aggregation. It has been known that matrix metalloproteinase-9 (MMP-9) is released from human platelets, and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GC to form an activated MMP-9 (86-kDa) on gelatinolytic activities. And then, GC dose-dependently inhibited platelet aggregation, intracellular Ca(2+) mobilization, and thromboxane A(2) (TXA(2)) formation in collagen-stimulated platelets. In addition, GC significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have an anti-platelet function in both resting and collagen-stimulated platelets. Therefore, we demonstrate that the inhibitory effect of GC on platelet aggregation might be involved into the following pathways. GC may increase intracellular cAMP and cGMP production and MMP-9 activity, inhibit intracellular Ca(2+) mobilization and TXA(2) production, thereby leading to inhibition of platelet aggregation. These results strongly indicate that GC is a potent inhibitor of collagen-stimulated platelet aggregation. It may be a suitable tool for a negative regulator during platelet activation.     

安步乐克对老年短暂性脑缺血发作患者体内血小板聚集和炎症因子的影响

目的：观察盐酸沙格雷酯片（安步乐克）降低老年短暂性脑缺血发作（TIA）患者体内血小板聚集率和炎症因子水平的效果。方法：选择40例TIA患者,随机平均分为2组。治疗组和对照组患者分别口服安步乐克和阿司匹林肠溶片各100mg,每日3次,连续服用（IL-6）、肿瘤坏死因子（TNF．d）水平。结果：用药后,治疗组和对照组血小板聚集率和炎症因子水平均较2周。治疗前和用药2周后空腹抽血测定血小板聚集率及高敏C反应蛋白（hs-CRP）、白介素6治疗前显著下降（P〈0．05,P〈0．01）,其中,治疗组血小板聚集率、hs-CRP、IL-6水平明显低于对照组（P〈0．05）,TNF．d水平则明显高于对照组（P〈0．01）。结论：安步乐克@可明显抑制老年TIA患者体内血小板聚集,降低hs．CRP、IL-6和TNF-a水平。     

Components of traditional Chinese medicine inhibit platelet aggregation by blocking ADP receptor subtypes P2Y_1 and P2Y_(12)

Platelets aggregation and thrombosis formation are major reasons of cardiovascular and cerebral vascular diseases.To develop new generative,potent and safe agents for inhibiting platelet aggregation and preventing above diseases are urgently required.Some traditional Chinese medicines of″Houxue Huayu″have been shown to inhibit platelet aggregation potently.In the present study the mechanisms and the molecular targets of puerarin,salvianolic acid B and the analogue of 3-n-butylphthalide,dl-PHPB were investigated and compared with ticlopidine.Four platelet aggregation inducers,ADP,arachidonic acid,collagen and thrombin were used in the study.It was found that puerarin and dl-PHPB specifically inhibited ADP induced platelet aggregation like ticlopidine did.However,salvianolic acid B inhibited both ADP and collagen induced platelet aggregations with similar potency.Due to existing two ADP receptor subtypes on platelets,P2Y1 and P2Y12,we studied the action of above compounds on the receptors and the signaling pathways.It was found that dl-PHPB decreased IP1 accumulation produced by ADP,but had no effect on IP1 level induced by m-3M3 FBS,an activator of PLC.M-3M3 FBS might attenuate the inhibitory effect of dl-PHPB on ADP-induced platelet aggregation.In addition,dl-PHPB did not affect cyclic AMP formation in platelets by ADP,which is different from P2Y12 antagonist ticlopidine.Puerarin showed the similar effects of dl-PHPB.Therefore,the actions of dl-PHPB and puerarin might be through P2Y1receptor-PLC-βpathway.Salvianolic acid B did not reduce the IP1 accumulation stimulated by ADP.It might act on the receptor subtype P2Y12.Our results suggest that components of Chinese herb medicine might be a resource for development of novel anti-platelet drugs.     

盐酸替罗非班对急性冠状动脉综合征患者血小板聚集率和C反应蛋白水平的影响

目的 观察盐酸替罗非班对急性冠状动脉综合征（ACS）患者血小板聚集率、C反应蛋白（CRP）水平的影响.方法 将102例ACS患者完全随机分为常规治疗组（51例）和替罗非班组（51例）.常规治疗组给予抗凝、抗血小板、调脂等常规药物治疗;替罗非班组在常规治疗的基础上,静脉滴注盐酸替罗非班48 h.治疗前后测定2组患者血浆二磷酸腺苷诱导的血小板聚集率、血清CRP水平,记录2组患者30 d随访期间心血管事件发生情况.结果 替罗非班组和常规治疗组治疗前血小板聚集率及血清CRP水平差异均无统计学意义[分别为（48±10）％比（50±12）％,（17.8±2.6） mg/L比（18.7±1.7） mg/L,均P＞0.05];替罗非班组和常规治疗组治疗后血小板聚集率及CRP水平分别为（12±6）％、（4.3±2.2） mg/L;（26±13）％、（9.3 ± 2.6） mg/L,均较治疗前明显下降（P＜0.01）;2组治疗后比较差异有统计学意义（P＜0.01）.随访30 d主要心血管事件心力衰竭、顽固性心绞痛发作、再发心肌梗死、全因死亡等,替罗非班组和常规治疗组比较差异均无统计学意义[2.0％ （1/51）比3.9％ （2/51）,3.9％ （2/51）比5.9％ （3/51）,0比2.0％（1/51）,0比0]（均P＞0.05）.治疗期间,2组均无出血不良反应及大出血并发症发生.结论 ACS患者应用盐酸替罗非班可更迅速、有效地抑制血小板聚集,并能降低CRP水平.     

Effect of 2(1-piperazinyl)-4H-pyrido[1,2-a]pyrimidin-4-one (AP155) on human platelets in vitro

The effect on human platelets of 2-(1-piperazinyl)-4H-pyrido[1,2-a]pyrimidin-4-one (AP155) was tested in vitro by measuring cyclic adenosine monophosphate (cAMP) level, cytosolic Ca⁺⁺, [¹²⁵I]fibrinogen binding as well as aggregation induced by several agonists. AP155 dose-dependently inhibited aggregation both in platelet rich plasma (PRP) and in washed platelets (WP), exerting its maximal power in the presence of collagen, ADP and platelet activating factor (PAF). It specifically inhibited the activity of cAMP high affinity phosphodiesterase (PDE), resulting in a sufficient increase in cAMP levels to activate cAMP-dependent protein kinase. AP155 was able to inhibit aggregation, the increase in cytosolic Ca⁺⁺ induced by thrombin, and fibrinogen binding to ADP or thrombin-stimulated platelets. Thus, this new pyridopyrimidine derivative exerts its antiplatelet activity by increasing cAMP intracellular concentration.     

山茱萸环烯醚萜苷对家兔、大鼠血小板聚集及出血时间的影响

目的：研究山茱萸环烯醚萜苷（CIG）对血小板聚集和出血时间的影响。方法：应用比浊法测定家兔（体外实验）及血瘀模型大鼠（体内实验）的血小板聚集率;断尾法观察大鼠出血时间。采用肾上腺素加冰水刺激法制备血瘀大鼠模型。结果：在体外实验中,CIG（0.75～3 mg/mL）能明显抑制二磷酸腺苷（ADP）或花生四烯酸（AA）诱导的家兔血小板聚集（P〈0.05,P〈0.01）,对血小板活化因子（PAF）诱导的血小板聚集无显著影响,但更大剂量（6～12 mg/mL）能抑制PAF诱导的血小板聚集（P〈0.01）。在体内实验中,CIG大剂量（180 mg/kg）灌胃给药能显著抑制ADP诱导的血瘀模型大鼠血小板聚集（P〈0.01）,延长正常大鼠的出血时间（P〈0.05）。结论：山茱萸环烯醚萜苷具有抗血小板聚集作用,大剂量能够延长出血时间。