单甘酯对实验性血栓形成的影响

目的　研究单甘酯 (glycolmannatesulfate ,GMS)对血栓形成的影响。方法　结扎大鼠下腔静脉观察对静脉血栓的形成 ,Chandler方法观察体外血栓形成 ,全自动凝血仪测定凝血指标和纤维蛋白原及ATⅢ、Ⅱ、Ⅱa活性。结果　GMS 2 0、40mg·kg-1对大鼠静脉血栓的形成有抑制作用 (P<0 0 1) ;2 5mg·kg-1即能明显抑制家兔体外血栓的形成 ,随剂量的增加而增强。GMS可使家兔TT、CT、APTT、RT及PT明显延长 ,降低大鼠血浆纤维蛋白原含量及降低因子Ⅱ及因子Ⅱa活性 ,升高ATⅢ活性。结论　GMS具有明显的抗血栓形成作用 ,其作用机制与其抗凝血作用有关     

溶栓1号抗血小板聚集及抗血栓形成作用

溶栓 1号是从蚯蚓中提取的酸性蛋白酶 ,并经进一步纯化 ,可静脉给药考察对ADP诱导的家兔血小板聚集的抑制作用 ;并采用小鼠肺血栓模型 ,电刺激致家兔颈动脉血栓模型及穿线法形成家兔颈动脉血栓模型 3种实验性血栓模型 ,考察溶栓 1号的抗血栓形成作用。实验结果表明 :溶栓 1号静脉注射给药 (1 5 0、3 0 0、60 0u/kg)可明显抑制ADP诱导的家兔血小板聚集作用 ,并可明显抑制小鼠肺血栓、家兔颈动脉血栓的形成。溶栓 1号抑制血栓形成可能与抑制血小板活性有关     

蛇床子素抑制血栓形成和血小板聚集的实验研究

目的　观察蛇床子素抑制血栓形成和血小板聚集的作用。方法　利用大鼠动-静脉旁路血栓形成模型和小鼠尾静脉注射胶原-肾上腺素合剂诱导血栓形成模型,分别测定给蛇床子素10、20、40mg·kg-1后血栓湿重和干重, 5min内小鼠死亡数和15min内偏瘫恢复数;分别采用ADP、凝血酶、花生四烯酸钠为诱导剂,测定经不同浓度蛇床子素处理后1、3、5min时血小板聚集率及最大聚集率的改变。结果　蛇床子素可以抑制大鼠动-静脉旁路血栓形成,减轻血栓湿重及干重;抑制胶原-肾上腺素合剂诱导的血栓形成,降低5min内的小鼠死亡率,提高15min内偏瘫小鼠的恢复率;蛇床子素在体外可抑制ADP、凝血酶、花生四烯酸钠诱导的血小板聚集,其IC50分别为0 .44、0 .186、0 .421g·L-1。结论　蛇床子素可明显抑制血栓形成和血小板的聚集。     

大鼠实验性血栓模型的建立及其应用

目的：建立不同的动物血栓模型，评价阿司匹林的抗血栓作用。方法：根据文献建立角叉菜胶诱发小鼠尾动脉血栓模型、动脉埋线诱发大鼠颈动脉血栓模型以及大鼠血小板聚集的体外实验模型等，并进行改进。结果：角叉菜胶诱发小鼠尾动脉血栓形成，血栓发生率为90％，血栓长度为（15．8&#177;1．9）mm，阿司匹林25～100mg&#183;kg^-1，可以剂量依赖性降低血栓发生率和缩短血栓长度缩短。阿司匹林还可以剂量依赖性抑制动脉埋线诱发大鼠颈动脉血栓形成，血栓质量分别由（3．7&#177;0．6）mg降低为（3．0&#177;0．6），（2．3&#177;1．3）。（1．8&#177;0．4）mg，并能降低血浆中6-keto-PGF1／TXB2的比值。同时阿司匹林还可以剂量依赖性抑制大鼠体外血小板聚集率。结论阿司匹林具有确切的抗血栓形成作用。     

中国眼镜蛇毒蛋白酶的分离、纯化及其对血小板聚集的影响

目的：从中国眼镜蛇毒中分高纯化出可水解纤维蛋白原的蛇毒蛋白酶,并观察其体内给药对血小板聚集的影响。方法：使用超滤的方法以及肝素亲和层析柱HeparinSepharoseCL－6B和凝胶层析柱SephadexG150分高纯化中国眼镜蛇毒蛋白酶。SDS-聚丙烯酰胺凝胶电泳（SDS－PAGE）检测其纯度和分子量。比浊法测定血小板聚集率。结果：从中国眼镜蛇毒中纯化出具有水解纤维蛋白原活性的蛋白酶,经SDS－PAGE电泳测定为一条带,分子量为47.1kD。该蛋白酶低剂量（0．025mg／kg）、中剂量（0．05mg／kg）以及高剂量（0．1mg／kg）体内给药后,剂量依赖性地抑制ADP（10μmol／L）、胶原（100μg／ml）诱导的兔血小板聚集。结论：具有水解纤维蛋白原活性的中国眼镜蛇毒蛋白酶在体内表现出抑制血小板聚集的作用。     

五步蛇毒纤溶酶FⅡ对LPS诱导的肾纤维蛋白沉积的作用

目的观察五步蛇毒纤溶酶FⅡ对LPS诱导的兔肾纤维蛋白沉积的作用。方法用脂多糖(LPS)诱导的兔肾血栓模型作为本实验的研究方法。生理盐水作阴性对照组;尿激酶作阳性对照组。兔肾组织学检查及测定血浆FDP含量以观察五步蛇毒纤溶酶FⅡ对兔肾纤维蛋白沉积的溶解作用。结果阴性对照组,给药2、6h后,兔肾组织有大量的纤维蛋白的沉积,FDP含量分别为(7821±479)%和(8427±621)%;阳性对照组,给药2、6h后,肾组织有少量纤维蛋白的沉积,FDP含量分别为(13334±427)%和(21017±542)%。FⅡ分别以01mg·kg-1·h-1(低)、03mg·kg-1·h-1(中)、06mg·kg-1·h-1(高)3个剂量滴注。低剂量组的兔肾组织有纤维蛋白的沉积,但比阴性对照组减少;中剂量组的兔肾组织有少量纤维蛋白的沉积;高剂量组的兔肾组织几乎无纤维蛋白的沉积;血浆FDP含量在低、中和高剂量组均比阴性对照组增加,并有量效关系(P<005)。结论步蛇毒纤溶酶FⅡ对LPS诱导的兔肾纤维蛋白沉积有良好的降解作用。     

补阳还五注射液对大鼠血液流变学及大鼠实验性血栓的影响

目的观察补阳还五注射液对大鼠血液流变学及实验性血栓的影响。方法用冰水浴刺激及肾上腺素应激法建立大鼠急性血瘀模型,观察补阳还五注射液静脉注射给药10、5、2.5 g.kg-1对大鼠血液流变学的影响;用大鼠动静脉旁路法建立实验性血栓模型,观察补阳还五注射液静脉注射给药10、5、2.5 g.kg-1对大鼠实验性动脉血栓的影响;体外法观察补阳还五注射液对腺苷二磷酸(ADP)诱导家兔体外血小板聚集率的影响。结果补阳还五注射液能降低全血黏度和血浆黏度;能对抗大鼠的实验性动脉血栓的形成,抑制ADP诱导家兔血小板聚集作用。结论补阳还五注射液具有较好的降低血液黏度、降低血小板的聚集率及抑制实验性血栓形成的作用。     

灯盏花乙素苷元对大鼠血栓形成和血液流变学的影响

目的:研究灯盏花乙素苷元对大鼠血栓形成、血小板聚集和血液流变学的影响。方法:大鼠连续灌胃灯盏花乙素苷元(100,50,25 mg.kg-1)7 d。电刺激大鼠颈动脉复制动脉血栓模型,记录血栓形成时间;结扎大鼠下腔静脉复制静脉血栓模型,记录血栓湿重和干重;采用0.5×10-4mol.L-1的二磷酸腺苷(adenosine d iphosphate,ADP)诱导血小板聚集,测定最大聚集率;大鼠皮下注射肾上腺素复制血瘀模型,测定红细胞沉降率、全血表观黏度和血浆黏度。同时设灯盏花乙素(100 mg.kg-1)阳性对照。结果:灯盏花乙素苷元能够明显延缓大鼠动脉血栓形成时间,抑制静脉血栓形成,抑制ADP诱导血小板聚集,降低血瘀模型大鼠的红细胞沉降率和血黏度。结论:灯盏花乙素苷元具有抗血栓形成、抗血小板聚集、改善血液流变学指标的作用,疗效优于灯盏花乙素。     

激活血管内皮细胞乙酰胆碱作用靶标的抗血栓作用及其分子机制

目的　在角叉菜胶诱发的小鼠尾动脉血栓模型上 ,研究激活血管内皮细胞乙酰胆碱作用靶标对血栓形成的影响并探讨其可能的分子机制。方法　比较既可激活血管内皮乙酰胆碱作用靶标 ,又可激活M受体的槟榔碱和仅可激活M受体的毛果芸香碱对成栓率和血栓长度影响的差异 ,分析激活内皮乙酰胆碱作用靶标对血栓的影响 ;通过测定血小板最大聚集率 ;凝血酶原时间 (PT)、活化部分凝血活酶时间(KPTT)和凝血酶时间 (TT) ;血浆中组织型纤溶酶原激活物(t PA)的含量和纤溶酶原激活物抑制剂 (PAI 1)的活性 ;血浆血栓素A2 (TXA2 )和前列环素 (PGI2 )含量 ,分析其可能的分子机制。结果　槟榔碱在 0 1～ 4 0mg·kg-1(ip)可剂量依赖性地对抗血栓形成 ,而在相同条件下 ,大剂量 (4mg·kg-1)的毛果芸香碱仍无抗血栓作用 ;槟榔碱对TT ,PT和KPTT和血小板最大聚集率 (MAR)均无影响 ;使血浆中t PA的含量升高 ,PAI 1的活性降低 ;使血栓形成过程中升高的TXA2 降低 ,并呈明显的量效关系 ,使血栓形成过程中降低的PGI2 升高。结论　激活血管内皮细胞乙酰胆碱靶标可对抗血栓形成 ,其可能的分子机制不通过直接影响凝血系统和血小板的聚集 ,而通过促进内皮细胞释放t PA和抑制内皮细胞合成并释放的PAI 1的活性 ,间接激活纤溶系统 ,发挥抗血栓?     

L—精氨酸L—门冬氨酸盐对血栓形成的影响及其机制

目的观察L-精氨酸L-门冬氨酸盐(DR)对动物血栓形成模型的影响并初步探讨其作用机制.方法用大鼠颈动脉血栓模型、动静脉旁路血栓模型和小鼠肺栓塞模型评价DR的抗血栓作用;测定血浆TXA2、PGI2和NO水平,测定血管内皮释放PGI2水平,以探讨DR的作用机制.结果DR7.5、15、30mg*kg-1单次灌胃给药,可减轻大鼠颈动脉血栓重量(P<0.01);7.5、15、30或60mg*kg-1均可显著抑制血小板在动静脉旁路中丝线上的沉积(P<0.05或P<0.01);但对花生四烯酸引起的小鼠肺栓塞死亡无明显作用.DR30mg*kg-1单次给药(ig),对大鼠血浆TXA2水平无明显影响;使PGI2有升高趋势.而相同剂量阿司匹林(ASA)可明显抑制二者水平.DR30mg*kg-1给药(ig)7次,每日2次,可明显促进血管内皮释放PGI2;并使血浆NO水平有明显升高.结论DR可明显抑制动脉血栓形成,其作用可能与血管内皮释放PGI2和NO有关,而与血小板花生四烯酸代谢途径无关.     

眼镜蛇毒蛋白酶natrahagin水解纤维蛋白原的特性及对人血小板聚集的

AIM: To study the fibrinogenolytic properties of natrahagin and its effect on platelet aggregation. METHOD: SDS-PAGE, fibrinogenolytic activity assay, platelet aggregation. RESULTS: Upon incubation of fibrinogen with natrahagin at the ratio of 50:1 (w/w), A alpha-chains of fibrinogen were almost completely hydrolyzed in 5 min; however, at least 6 h was needed for the complete degradation of gamma-chains. Fibrinogenolytic activity of natrahagin was 0.349 +/- 0.044 g.min-1.g-1 as determined by its ability to reduce the clottable fibrinogen. On the other hand, natrahagin concentration-dependently inhibited platelet aggregation induced by ristocetin in platelet-rich plasma and thrombin (80 U.L-1) in washed platelets with IC50 (95% confidence limit) of 56 (40-79) and 3.3 (1.4-8.0) mg.L-1. No inhibitory effect was found on collagen- and ADP-induced platelet aggregation even when the dose of natrahagin reached 200 mg.L-1. CONCLUSION: Natrahagin is an alpha, gamma-fibrinogenase with an inhibitory effect on platelet membrane glycoprotein Ib (GPIb)-dependent platelet aggregation.     

甲基黄酮醇胺对血小板花生四烯酸代谢通路的影响

甲基黄酮醇胺(MPA)40mg·Kg~(-1)iv,能使花生四烯酸(AA)诱发的小鼠死亡率降低61％.MFA12.5～200μmol·L~(-1)呈剂量依赖性地抑制AA诱导的免血小板聚集.聚集率为49％±10％～4％±4%,对照组为69％±3％.MFA0.1～0.4mmol·L~(-1)呈剂量依赖性抑制AA诱导兔的血小板丙二醛(MDA)的生成,为(nmol·10~(-9)血小板)0.075±0.011～0.111±0.023,对照组为0.170±0.017.MFA0.4 mmol·L~(-1)有效地抑制凝血酶和A A诱导的兔血小板内MDA生成.分别为0.016±0.006.0.080±0.017,对照组分别为0.048±0006,0.160±0.025;普萘洛尔仅抑制凝血酶诱导的MDA生成.对AA诱导的MDA无影响.MFA0.4mmol·L~(-1)不影响血小板内cAMP含量.结果提示MFA抑制血小板AA代谢通路可能是其抑制血小板聚集功能的机理之一.     

异亚丙基莽草酸抗血栓作用的实验研究

目的研究异亚丙基莽草酸(ISA)对大鼠动静脉环路血栓、大脑中动脉栓塞及血小板聚集的对抗作用及机制。方法用动静脉环路血栓及三氯化铁致大脑中动脉栓塞(MCAT)模型观察药物作用;并研究了ISA体内、外给药对血小板聚集的影响。结果ISA 25,50,100及200 mg·kg^-1 ig均可显著降低大鼠体外血栓重量;ISA 50,100,200 mg·kg^-1 ig可明显改善MCAT模型大鼠神经症状;ISA 100及200 mg·kg^-1 ig MCAT模型大鼠脑梗塞范围分别下降27.8%和31.6%;另外,ISA体内、外给药对ADP和胶原诱导的血小板聚集有明显的抑制作用。结论ISA可能通过抗血小板聚集作用抑制血栓的形成。     

人参,西洋参及三七总皂甙对大鼠血小板功能及血栓形成的抑制作用

体外试验表明人参总甙(SPG),西洋参总甙(SPQ)和三七总甙(SPNG)均能抑制胶原诱导的大鼠血小板聚集,其IC_(50)分别为0.583,1.012及0.815mg·ml~(-1),对胶原诱导引起的血小板5-HT释放,在0.5mg·ml~(-1)时,SPG,SPQ及SPNG的抑制率分别为20％,4％及16％,对血小板内cAMP含量,在35mg·kg~(-1)iv后,SPG,SPQ及SPNG均能使其显著增加.体内试验,对大鼠的实验性血栓,SPNG在80mg·kg~1 ig 1.5～2 h后有显著的抑制作用,但同样剂量的SPG无效Rg_1 20mg·kg~1 ig能显著抑制血栓形成,iv能显著抑制凝血酶所致DIC的血小板数目减少,FDP的增加,但对纤维蛋白原,凝血酶原时间的改变则无明显的拮抗作用。     

Inhibitory effect of a selective thromboxane A2 receptor antagonist, EP 092, on platelet aggregation in whole blood ex vivo and in vivo.

1. The inhibitory effect of a selective prostaglandin H2 (PGH2)/thromboxane A2 receptor antagonist, EP 092, on platelet aggregatory responses in whole blood ex vivo (guinea-pig: Rhesus monkey) and intravascular aggregation in vivo (rabbit) has been investigated. 2. Collagen (0.1-10.0 micrograms ml-1) caused a concentration-dependent decrease in single platelet count in samples of both guinea-pig and Rhesus monkey citrated whole blood incubated ex vivo. EP 092 administered to guinea-pigs by intravenous (0.1-3.0 mg kg-1) or oral (1.0-10.0 mg kg-1) routes significantly inhibited the platelet responses to collagen (ED50 values 1.3 +/- 0.2 and 1.4 +/- 0.2 mg kg-1 respectively). Similar potency against collagen-induced whole blood aggregation was observed in Rhesus monkey blood samples following EP 092 given orally (ED50 0.9 +/- 0.3 mg kg-1). 3. The duration of action of EP 092 against collagen aggregatory responses ex vivo in both guinea-pigs and Rhesus monkeys was between 3 and 6 h following oral administration at 3.0 mg kg-1. 4. The inhibitory activity demonstrated by EP 092 against collagen-induced aggregation of Rhesus monkey whole blood ex vivo was not accompanied by any significant reduction in thromboxane A2 formation except at the highest dose tested (10 mg kg-1). 5. The intravascular aggregatory response induced by collagen or thrombin in the anaesthetized rabbit was significantly inhibited by an intravenous infusion of EP 092 (10 mg kg-1). EP 092 appeared less potent and its effect was of shorter duration in this preparation compared with its inhibitory effect on ex vivo aggregation, being evident immediately after infusion of drug but not after a further 30 min. 6. It is concluded that collagen-induced platelet aggregatory response in guinea-pig and Rhesus monkey whole blood ex vivo and rabbit in vivo exhibit a thromboxane-dependent component which can be inhibited in a dose-related fashion by pretreatment with the thromboxane antagonist EP 092. In the rabbit, moreover, the data support the possibility of a role for thromboxane in the intravascular aggregatory response to thrombin.     

丁基苯酞对大鼠血栓形成及血小板功能的影响

目的研究消旋、左旋和右旋丁基苯酞(dl-,l-和d-NBP)对血栓形成及血小板功能的影响。方法利用半体外血栓形成术及比浊法,观察dl-,l-和d-NBP及阿司匹林(Asp)对大鼠血栓湿重和血小板聚集率的影响,并用放免法、荧光分光光度法测定其对血小板内cAMP和TXB2的水平以及血小板5-HT释放率的影响。结果ip,dl-NBP和l-NBP可剂量依赖性地抑制大鼠血栓形成,且l-NBP作用与Asp相似,d-NBP对半体外血栓形成无显著作用;dl-,d-和l-NBP可显著抑制胶原、ADP、花生四烯酸诱导的血小板聚集。结论NBP有抗血栓作用,l-NBP作用最强,dl-NBP作用较弱,其抗栓作用与升高血小板内cAMP的含量及抑制5-HT释放有关。     

盐酸非洛普对人和兔血小板聚集的影响

用比浊法和放射免疫法分别测定盐酸非洛普对兔和人血小板聚集及兔血栓素Ａ２（ＴＸＡ２）和动脉壁前列环素（ＰＧＩ２）含量的影响。盐酸非洛普呈剂量依赖性抑制ＡＤＰ（ＩＣ５０＝５．８×１０－４ｍｏｌ·Ｌ－１）和ＡＡ诱导的兔血小板聚集。对ＡＤＰ和Ａｄｒ诱导的人血小板聚集亦有明显抑制作用且呈剂量依赖性，ＩＣ５０值分别为１．２和１．３×１０－４ｍｏｌ·Ｌ－１。盐酸非洛普短期应用（８ｍｇ·ｋｇ－１ｉｖｔｉｄ×２ｄ）明显抑制ＡＤＰ和ＡＡ诱导的兔血小板聚集及ＴＸＢ２的产生和释放，对兔动脉壁和血浆６－ｋｅｔｏ－ＰＧＦ１α含量无显著影响。研究结果表明，盐酸非洛普抗血小板聚集作用与其抑制血小板ＴＸＡ２合成和释放有关，亦可能与其α２受体阻断作用有关。     

The inhibitory effect of liposome-encapsulated indomethacin on inflammation and platelet aggregation

A comparison has been made between liposome-encapsulated and free indomethacin for their anti-inflammatory activities in the carrageenan paw oedema test in rats, and their inhibitory effect on platelet aggregation induced by adenosine 5-diphosphate (ADP) in-vitro. Free indomethacin, 3 mg kg-1, strongly inhibited carrageenan-induced oedema and a similar inhibitory activity was shown by 0.3 mg kg-1 of encapsulated drug. For the inhibition of platelet aggregation, the threshold concentration of free drug was 0.559 mM. At this concentration, at least 5 min incubation was needed to achieve 12.5% and 45 min for 50% inhibition. The inhibition was much stronger with encapsulated drug, and pre-incubation of 28 microM encapsulated drug for 10 min with platelet-rich plasma before addition of ADP completely inhibited platelet aggregation.     

Effects of GP IIb/IIIa receptor inhibitor tirofiban (aggrastat) in ex vivo canine arteriovenous shunt model of stent thrombosis

The authors investigated the effects of the platelet glycoprotein IIb/IIIa platelet inhibitor, tirofiban, on stent thrombosis in an ex vivo canine arteriovenous shunt model of high-shear blood flow. Control nitinol stents (n = 64) were expanded to 2 mm in diameter in a tubular perfusion chamber interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100/s for 20 min (n = 385 perfusion runs). Seven animals were treated with intravenous tirofiban (0.3, 3.0, and 30.0 microg x kg-1x min-1) with or without heparin (50 U/kg). Effects on thrombus weight, platelet aggregation, platelet P-selectin expression, bleeding time, D-dimer levels, and activated clotting time were quantified. Dethrombotic and antithrombotic effects were examined in stents with and without preformed thrombus, respectively. Tirofiban alone produced a dose-dependent reduction in preformed stent thrombus weight with 21% +/- 20% and 36% +/- 15% inhibition at 3- and 30-microg x kg-1x min-1 doses, respectively (P < 0.01). De novo stent thrombus formation was inhibited by 80% at 0.3 and >95% at 3- and 30-microg x kg-1x min-1 doses, respectively (all P < 0.001). Treatment with heparin and tirofiban produced no incremental inhibitory effect on stent thrombosis compared with tirofiban alone, except for the antithrombotic effect observed with the 0.3 microg x kg-1x min-1 dose. The inhibitory effects of tirofiban were associated with >95% suppression of platelet aggregation at 0.3 microg x kg-1x min-1 and complete inhibition at higher doses. Bleeding time was prolonged from 3.5 +/- 1.0 to 13 +/- 6 min at the 0.3 microg x kg-1x min-1 dose and >30 min at higher doses, but activated clotting time and circulating platelet P-selectin expression remained unchanged with tirofiban. A modest but significant platelet deaggregation effect and an increase in plasma D-dimer levels were observed with tirofiban at the 30-microg x kg-1x min-1 dose. Thus, tirofiban produced a dose-dependent dethrombotic effect on stent thrombosis and inhibited acute de novo stent thrombosis under high-shear flow conditions.