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。     

钩藤碱对血小板聚集和血栓形成的影响

钩藤碱(Rhy)明显抑制AA,胶原及ADP诱导的大鼠血小板聚集。Rhy不影响血小利用外源性AA合成TXA_2,但抑制胶原诱导的TXA_2生成;在抗血小板聚集有效剂量时,对PGI_2的生成无影响。Rhy有显著降低血栓形成诱导剂ADP及胶原加肾上腺素静脉注射所致小鼠死亡率。     

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。     

3,4-二羟基苯乙酮对家兔血小板释放血栓素A2的影响

3,4-二羟基苯乙酮(DHAP)俸内体外给药,都明显抑制胶原或花生四烯酸诱导家兔血小板释放的血栓素B₂含量,剂量与效应相关,生物测定法与放射免疫分析所得结果相平行。实验结果还表明,AA较胶原诱导血小板释放TXB₂量强3～6倍。如不加诱导剂,血小板自发性释放TXB₂量甚微。此外,DHAP抑制AA诱导血小板释放TXB₂的作用也较胶原诱导时为强。DHAP是环加氧酶抑制剂,还是TXA₂合成酶抑制剂,有待进一步证实。     

蝙蝠葛碱对血小板聚集及花生四烯酸代谢的影响

蝙蝠葛碱(Dau) 抑制AA及ADP诱导的大鼠血小板聚集,也能抑制AA,ADP及Adr诱导的人血小板聚集。这种抑制作用与Dau剂量呈依赖关系。Dau抑制大鼠洗涤血小板对[1-¹⁴C]AA经环氧酶途径的代谢,TXB₂与HHT的形成均呈剂量依赖性减少。当Dau浓度达到0.1 mmol/L时亦能抑制12-HETE的形成。Dau对AA代谢的上述影响可能是其抑制血小板聚集的机理之一。     

莽草酸对血小板聚集和凝血的抑制作用

目的：研究莽草酸(SA)对血小板聚集性的影响及其机制,并研究其对凝血时间的影响。 方法：采用比浊法测定血小板聚集功能,放射免疫法测定血小板TXB2和血浆6-keto-PGF_1α水平,玻管法测定凝血时间。结果：SA体外呈浓度依赖性抑制ADP、胶原诱导的兔血小板聚集,IC₅₀分别为9.25, 3.56 mmol.L^-1;在体内(ip)抑制脑血栓模型鼠由ADP诱导的血小板聚集; SA促进大鼠血浆6-keto-PGF_1α的生成并延长小鼠凝血时间。结论：SA对血小板聚集及凝血系统有显著的抑制作用。     

咪苯嗪酮对TXA2和HHT生成的选择性抑制作用

咪苯嗪酮(CI-914)能抑制大鼠血小板环氧酶和TXA₂合成酶产物HHT的生成,而对脂氧酶产物12-HETE的生成仅高浓度药物才有弱的抑制作用,提示CI-914主要影响花生四烯酸(AA)环氧酶途径,而对脂氧酶途径影响较少。在大鼠血小板和中性白细胞CI-914能抑制TXA₂的生成,同时CI-914还可使白细胞6-keto-PGF_1a和血小板PGE₂的产生量显著增加,提示CI-914在这两种细胞引起了AA的转向合成。上述结果基本证实,CI-914在大鼠中性白细胞和血小板对TXA₂合成酶具有选择性抑制作用。     

小檗碱对局灶性脑缺血大鼠血小板聚集及血浆TXB2和6-keto-PGF1a水平的影响

以大鼠可逆性大脑中动脉梗塞(MCAO)致局灶性脑缺血为模型,观察小檗碱对大鼠MCAO24h后血小板粘附、聚集、血栓形成及血浆TXB2和PGI₂生成的影响。结果表明,小檗碱20mg·kg^-1·d^-1ipl,3或5d,明显降低MCAo24h后血小板粘附性及ADP、胶原和花生四烯酸诱导的血小板聚集率,抑制血浆TXB₂水平。同剂量ip3或5d,则抑制血栓形成。提示小檗碱可能通过其抗血小板粘附和聚集及影响花生四烯酸代谢而发挥抗脑缺血作用。     

甲基莲心碱及与牛磺酸合用对大鼠血小板聚集和血栓形成的影响

甲基莲心碱(Nef)ig抑制大鼠血栓形成,单用Nef及与牛磺酸(Tau)合用抑制率分别为53.31%和74.30%;对ADP、胶原、凝血酶诱导的血小板聚集抑制率,Nef及Nef+Tau分别为55.8%和73.4%,43.45%和59.3%,65.33%和78.5%。两药对血浆纤维蛋白原、优球蛋白溶解时间均无明显影响。Nef能有效抑制ADP诱导的血小板TXA₂释放,与Tau合用抑制作用增强,而对血浆PGI2含量无作用,Nef在iv后30min内对大鼠血清总胆固醇含量亦无影响,但与Tau合用后能降低血清总胆固醇水平。     

4-{[2-(1H-咪唑基)-1-(4-取代苯基)乙氧基]甲基}苯甲酸类化合物的合成及其抑制血小板聚集的作用

根据咪唑类和吡啶类TXA₂合成酶抑制剂的构效关系和作用机制,设计合成了20个4-{[2-(1H-咪唑基)-1-(4-取代苯基)乙氧基]甲基}苯甲酸类化合物。初步体外药理试验结果表明,所有化合物都有不同程度的抑制TXA₂合成酶能力,从而抑制花生四烯酸(AA)诱导的血小板聚集。化合物15的抑酶活性最强,以IC₅₀值相比,其活性为Dazoxiben的55.6%。并初步探讨了这类化合物的构效关系。     

Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis

In vitro and ex vivo effects of 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (diferuloylmethane, curcumin) and acetylsalicylic acid (ASA) on the synthesis of prostacyclin (PGI2) and on platelet aggregation has been studied in rat. Both drugs inhibited adenosine diphosphate (ADP)-, epinephrine (adrenaline)- and collagen-induced platelet aggregation in monkey plasma. Pretreatment with ASA (25-100 mg/kg), but not curcumin (100-300 mg/kg), inhibited PGI2 synthesis in rat aorta. In the in vitro system, too, curcumin caused a slight increase in the synthesis of PGI2, while ASA inhibited it. Curcumin may, therefore, be preferable in patients prone to vascular thrombosis and requiring antiarthritic therapy.     

Regulation of human platelet activation--analysis of cyclooxygenase and cyclic AMP-dependent pathways

We have studied the regulation of human platelet activation by cyclic AMP (cAMP), and the cyclooxygenase products by examining the effect of prostacyclin (PGI2) and indomethacin on platelet aggregation, release reaction and thromboxane B2 (TxB2) generation induced by the full dose range of common platelet agonists in both platelet-rich plasma and washed platelets. Platelet aggregation, [14C]-5HT and TxB2 release induced by "threshold" and "supramaximal" concentrations of ADP, adrenaline, platelet-activating factor (PAF) and U46619 were totally abolished by low concentrations of PGI2 (3-6 nM). In contrast, platelet activation induced by submaximal concentrations of collagen, thrombin and the calcium ionophore A23187 was only partially inhibited by PGI2 (3-3000 nM). PAF-induced release reaction like that induced by ADP and adrenaline was totally dependent on the cyclooxygenase products and aggregation, while U46619-induced release reaction was only partially dependent on aggregation and the cyclooxygenase products. While both PGI2 (18-3000 nM) and indomethacin (10 microM) abolished collagen-induced aggregation and the aggregation-mediated release reaction, neither inhibitor significantly inhibited platelet adhesion or the adhesion-mediated release reaction. Maximal thrombin-induced aggregation and release reaction was also not significantly inhibited by PGI2 (300 nM) or indomethacin (10 microM). Thromboxane (TxB2) generation induced by sub-maximal to maximal concentrations of collagen, thrombin and A23187 was, although significantly inhibited, not abolished by PGI2. These results demonstrate that PAF is a "weak" agonist similar to ADP and adrenaline, U46619 is an agonist intermediate between weak and strong which induces a release reaction that is only partially dependent on aggregation, but unlike the strong agonists, is totally susceptible to inhibition by PGI2, PGI2 is an indirect inhibitor of phospholipase activation, which does not significantly inhibit non-aggregation-mediated arachidonate mobilization, induced by the strong agonists, and the so-called third pathway in the collagen and thrombin-induced release reaction, which is insensitive to indomethacin, is also insensitive to elevators of cAMP such as PGI2.     

Effect of fibrinopeptides A and B on human and rat platelet aggregation in vitro

The effect of fibrinopeptides on platelet aggregation is reported. Fibrinopeptide A (minimal effective concentration, 0.65 microM) aggregated human (but not rat) platelets suspended in plasma and at lower concentrations (0.01-0.1 microM) potentiated platelet aggregation due to ADP and collagen in both species. Fibrinogen mimicked these effects of fibrinopeptide A. P-bromophenacyl bromide (100 microM), mepacrine (10 microM), indomethacin (10 microM) and dazoxiben (10 microM) inhibited human platelet aggregation induced by fibrinopeptide A and fibrinogen. In both species, fibrinopeptide B (0.65-6.5 microM) antagonised the platelet inhibitory effect of PGI2 and PGD2 but not adenosine. Antagonism was non-competitive in nature. The concentration of fibrinopeptide A required to potentiate platelet aggregation occurs naturally in the plasma of patients with thrombotic disease suggesting this effect may be of physiological significance during the formation of a thrombus. The novel action of fibrinopeptide B to reduce the platelet inhibitory effect of PGI2 and PGD2 may also contribute to the control of thrombus formation.     

阿斯匹林与维拉帕米并用对血小板聚集和血栓形成的影响

ASA与Ver对ADP诱导的兔体外血小板聚集和大鼠半体内血小板聚集均有明显的抑制作用,且呈量效关系。两者合用作用增强。ASA与Ver均能明显延长电刺激大鼠颈动脉血栓的形成时间,减少胶原和肾上腺素复合诱导剂静脉注射所引起的小鼠肺血栓形成的死亡。剂量与效应相关。两者合用作用增强。     

Effects of AVS (1,2-bis(nicotinamido)propane) on platelet function and vascular endothelium

The effects of 1,2-bis(nicotinamido)propane (AVS) on platelet function and vascular endothelium were investigated using various experimental thrombosis and vascular endothelial injury models. Neither in vitro platelet aggregation induced by ADP, collagen or arachidonate nor ex vivo platelet aggregation by ADP or collagen could be antagonized by AVS. On the other hand, AVS prevented mice, rats and rabbits from death induced by acute cerebral or pulmonary thromboembolism following the injection of arachidonate or collagen. These activities were as potent as those of acetylsalicylic acid. The disrupting actions of citrate and/or lipidperoxide (13-hydroperoxy linoleic acid) on endothelium were well inhibited by the pretreatment of AVS. AVS did not inhibit cyclooxygenase, increased prostacyclin (PGI2)/thromboxane A2 (TXA2) ratio in the coupled system of platelets and aortic microsomes. In conclusion, AVS inhibited thrombus formation in vivo while it was ineffective in vitro platelet alone system, which may result from the actions of this agent on both platelets and vascular endothelium. The above-mentioned results clearly show that AVS may be a new potent anti-vascular damaging agent with both endothelium stabilizing and PGI2 enhancing activities.     

6-Keto-prostaglandin E1 inhibits the aggregation of human platelets.

6-Keto-prostaglandin E1 (6-keto-PGE1) was found to have a similar potency to prostacyclin (PGI2) as an inhibitor of platelet aggregation. It caused a time and concentration dependent inhibition of ADP, collagen and epinephrine induced platelet aggregation, the dose ratios for 70% inhibition by 6-keto-PGE1, PGI2 and PGE1 being approximately 1 : 1 : 13. In doses similar to those of PGI2, 6-keto-PGE1 partially inhibited the release of [3H]-serotonin from platelet-rich plasma induced by collagen.     

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。     

Differential effect of platelet inhibitors in normal and in hypercholesterolaemic subjects.

Dibutyryl cyclic AMP, forskolin, dipyridamole and butyl imidazole inhibited platelet aggregation (induced by ADP or collagen) in washed platelets more than in platelet-rich plasma preparations. Aspirin, indomethacin and epoprostenol (prostacyclin, PGI2) showed no preferential inhibition of these platelet preparations. When platelet-rich plasma from either normal or familial hypercholesterolaemic (FH) subjects was used, aspirin, indomethacin and dipyridamole (but not forskolin) inhibited platelet aggregation in normal subjects more than in FH patients. When low doses of aspirin (75 mg daily for 7 days) or dipyridamole (250 mg, single dose) were administered in vivo, platelet aggregation was inhibited more in the normal subjects in comparison to the patient group.