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1.
银杏总内酯抗血小板聚集与抗血栓作用   总被引:11,自引:0,他引:11  
目的:探讨银杏总内酯抗血栓形成及抑制血小板聚集的作用.方法:采用大鼠动静脉旁路血栓模型和Chandler氏血栓形成法,利用血小板活化因子(platelet activating factor,PAF)、花生四烯酸(arachidonic acid,AA)和二磷酸腺苷(adenosine diphosphate,ADP)诱导家兔血小板聚集,测定血栓形成抑制率、血小板在不同时间点的聚集率以及最大聚集率.结果:银杏总内酯可不同程度地抑制大鼠动静脉旁路血栓和Chandler氏体外血栓形成,减轻血栓重量,血栓形成抑制率分别达到 41.58%和 59.31%;银杏总内酯可抑制PAF和ADP诱导的家兔血小板在不同时间点的聚集,降低其最大聚集率.结论:银杏总内酯可明显对抗血栓形成,并具有显著的抗PAF和ADP诱导血小板聚集作用.  相似文献   

2.
烟酰水杨酸对Collagen、ADP、AA诱导的兔血小板聚集的影响   总被引:2,自引:1,他引:2  
目的观察烟酰水杨酸(NSA)对Collagen、ADP、AA诱导的兔血小板聚集的影响。方法用比浊法测定了NSA体外、体内对兔血小板聚集的影响。结果NSA能明显抑制体外、体内Collagen、ADP诱导的血小板聚集,体外最大抑制率分别为55.7%、61.3%,体内最大抑制率分别为42.2%、74.8%。NSA对AA诱导的兔血小板聚集没有影响。结论NSA具有抑制Collagen、ADP诱导的血小板聚集的作用。其抑制作用具有明显的量效关系。  相似文献   

3.
目的 研究银杏内酯B(GB,抗血小板聚集)抑制血小板活化因子(PAF)介导的中性粒细胞活化.方法 将银杏内酯B加入抗凝全血中,阻断PAF对中性粒细胞活化;用PAF及二磷酸腺苷(ADP)活化下述各组的中性粒细胞,包括对照组、PAF组、PAF+GB组、ADP组和ADP+GB组,用流式细胞术检测中性粒细胞整和素(CD11b)平均荧光强度.结果 PAF及ADP均可明显增加中性粒细胞CD11b的平均荧光强度,银杏内酯B可明显抑制PAF及ADP诱导的CD11b的平均荧光浓度.结论 银杏内酯B可明显抑制PAF介导的中性粒细胞活化.  相似文献   

4.
花生壳提取物对家兔血小板聚集的影响   总被引:1,自引:0,他引:1  
闫文亮 《中国药房》2010,(31):2896-2897
目的:研究花生壳提取物体内、外给药对血小板活化因子(PAF)诱导家兔血小板聚集的影响。方法:分别采用体内和体外给药,比浊法测定血小板的聚集率,观察花生壳提取物对PAF诱导的家兔血小板聚集的抑制作用。结果:花生壳提取物在20、10mg·mL-1浓度下体外给药对PAF诱导血小板聚集有明显抑制作用(P<0.05),抑制率分别为47.13%、33.48%;在100mg·kg-1剂量下体内给药对PAF诱导血小板聚集有明显抑制作用(P<0.01),抑制率为21.78%。结论:花生壳提取物对PAF诱导的血小板聚集有抑制作用,其作用机制可能与拮抗PAF受体有关。  相似文献   

5.
目的 观察银杏内酯注射液、银杏内酯ABC以及银杏叶提取物注射液(EGb761)对家兔血小板聚集功能、超微结构及PF-4和β-TG含量的影响比较。方法 将日本大耳兔分为对照(生理盐水)组、EGb761(1.02 mL/kg)组、银杏内酯ABC (5.13 mg/kg)组、银杏内酯注射液(1.02 mL/kg,以萜内酯计5.1 mg/kg)组、白果内酯(5.13 mg/kg)组,分别iv相应药物1周。给药结束后,家兔心脏取血,观察PAF诱导下血小板聚集率;电镜观察血小板超微结构;试剂盒法观察PAF诱导下血清中血小板因子-4(PF-4)和β-血小板球蛋白(β-TG)含量。结果 与对照组比较,EGb761组、银杏内酯ABC组、银杏内酯注射液组的血小板聚集率均显著降低(P<0.05、0.01),白果内酯组无显著变化;血小板聚集抑制率:银杏内酯注射液(43.76%) > 银杏内酯ABC (35.3%) > EGb761(26.52%) > 白果内酯(5.48%)。与对照组比较,EGb761、银杏内酯ABC、银杏内酯注射液均能减少聚集型血小板数量,使树突型血小板突起变少变短。与对照组比较,银杏内酯注射液和银杏内酯ABC均使PF-4和β-TG表达显著降低(P<0.01),EGb761仅显著降低β-TG表达(P<0.05)。结论 银杏内酯注射液通过PAF途径发挥抗血小板聚集作用,其作用强于银杏内酯ABC,可能是白果内酯发挥了协同增效作用。  相似文献   

6.
目的考察银杏内酯B前体药物(PGB)的脑靶向性,并探究其靶向机制。方法采用LC-MS/MS考察大鼠尾静脉注射PGB后的脑部药动学规律并评价其脑靶向性;采用伊文斯蓝法观察PGB对不完全性脑缺血小鼠脑毛细血管通透性的影响;HPLC法测定PGB在正辛醇-水体系的分配系数(log P);MVD分子对接软件计算PGB与P-糖蛋白(P-gp)的体外结合力;定磷法检测PGB对人P-gp膜ATP酶活性的影响。结果以治疗有效性和靶向指数评价PGB的脑靶向效率达6.87和4.14;PGB预防给药可有效降低不完全性脑缺血小鼠的脑毛细血管通透性(P<0.05);PGB的log P为1.03,高于GB的0.61;分子对接计算表明PGB与P-gp结合力大于GB,其Mol Dock Score分别为-143.36、-116.40 KJ·mol-1;ATP酶活性分析提示PGB、GB均能提高P-gp ATP酶活性,其Km值分别为237.75、841.24μmol·L-1,PGB与P-gp亲和力高于GB。结论 PGB具有脑靶向性,其靶向性提高一方面得益于其脂溶性提高,PGB在脑部渗透量增加;另一方面可能为PGB明显提高P-gp ATP酶活性,从而抑制P-gp对GB的外排作用。  相似文献   

7.
目的:探讨异莲心碱(isoliensinineI,L)对大鼠体内血小板聚集和凝血功能的影响。方法:以二磷酸腺苷(ADP)诱导血小板聚集,采用比浊法观察IL对兔体内外血小板13,5,min聚集率和最大聚集率的影响,同时评价IL对大鼠凝血酶原时间(PT)、活化部分凝血激酶时间(APTT)及凝血酶时间(TT)的影响。结果:IL 4 mg.L-1和8 mg.L-1能显著抑制ADP诱导的兔体外血小板13,5,min聚集率和最大聚集率,其抑制率为14.4%和27.9%;IL 5 mg.kg-1和10 mg.kg-1能显著抑制ADP诱导的兔体内血小板1,35,min聚集率和最大聚集率,其抑制率为20.0%和32.6%;IL能显著延长大鼠PT、APTT和TT。结论:IL具有对抗血小板聚集和凝血作用。  相似文献   

8.
银杏内酯B抑制血小板CD40Ligand表达的分子机制研究   总被引:1,自引:0,他引:1  
目的探讨银杏内酯B(ginkgolide B)对活化血小板CD40 Ligand(CD40L)的影响以及相关的分子机制。方法取正常人血分离血小板,用不同浓度银杏内酯B孵育血小板5 min,然后用胶原(collagen)刺激血小板活化。用Westernblot分析PI3K表达,Akt磷酸化,CD40L的变化。结果①用collagen刺激血小板聚集,银杏内酯B(0.2、0.4、0.6 g.L-1)预处理血小板5 min,血小板聚集率明显降低,聚集率分别为77%,60%和48%。②Western blot结果显示胶原刺激血小板活化后CD40L表达明显增加,银杏内酯B以剂量依赖方式抑制了CD40L表达。③银杏内酯B对胶原刺激的血小板PI3K表达无明显影响。④collagen刺激血小板活化后Akt的磷酸化增加,银杏内酯B抑制了Akt磷酸化。结论银杏内酯B能够有效抑制collagen诱导的血小板聚集以及CD40L的表达,并明显抑制了Akt磷酸化,表明银杏内酯B能够通过PI3K/Akt信号传导通路抑制血小板活化。  相似文献   

9.
目的:探讨粉防己碱(Tet)对兔血小板聚集和PAF生成的影响.方法:卡西霉素(Cal)和PAF诱导血小板聚集的聚集率和Tet对血小板聚集的抑制率被测定;给予或未给予Tet处理之血小板用Cal刺激释放PAF的量也被测定.结果:在4—64 μmol·L~(-1)浓度范围,Tet明显抑制Cal和PAF诱导的血小板聚集.IC_(50)值分别为8.6μmol·L~(-1)和14.0μmol·L~(-1).Tet也浓度依赖性的抑制Cal诱导血小板释放PAF,IC_(50)值为21.0μmol·L~(-1).结论:Tet抑制血小板聚集作用与抑制内源性PAF生成有关.  相似文献   

10.
银杏叶片主要是以银杏树的叶片为原料,提取其中具有药理活性的物质:银杏总黄酮类,银杏苦内酯,用来治疗心、脑血管病症的一种新型药物,现将其作用机制及应用简介如下:1 作用机制1.1 人体内有一种很强的引发血小板聚集和形成血栓的内源性物质——血小板活化因子(PAF),能引起血栓,而银杏叶片中的主要成分银杏总黄酮甙及银杏苦内酯是PAF的克星,故具有阻止血小板聚集和血栓形成的作用。1.2 银杏叶片中的银杏黄酮甙和银杏苦内酯,此外,还能减少血中甘油三酯、血浆过氧化脂质,提高高密度脂蛋白的含量,提高清除自由基功能的红细胞超氧化物歧化…  相似文献   

11.
12.
目的观察金雀异黄酮对血小板聚集的影响,并初步探讨其作用机制。方法制备家兔富血小板血浆和贫血小板血浆,并通过加入不同浓度的金雀异黄酮,测定其对凝血酶和血小板活化因子(PAF)诱导的血小板聚集的抑制作用;并测定其对凝血酶的抑制率及PAF诱导聚集下的血栓素(TXB2)、6-酮-前列腺-F1α(6-Keto-PGF1α)的水平。结果金雀异黄酮能明显抑制由凝血酶和PAF诱导的血小板聚集,且金雀异黄酮与凝血酶有一定的亲和力,在PAF诱导的血小板聚集中,金雀异黄酮能明显降低TXB2水平,升高6-Keto-PGF1α水平。结论金雀异黄酮能够明显抑制由凝血酶和PAF诱导的血小板聚集,其作用与抑制凝血酶有一定关系外,可能与其通过调节PAF诱导聚集TXA2和PGI2的释放有关。  相似文献   

13.
This study was carried out to design and synthesize 10-O-nicotinate ginkgolide B (PGB) as a new prodrug of ginkgolide B (GB). The lipophilicity of PGB and GB was evaluated through the partition coefficient in 1-octanol–water system. The concentrations of PGB and GB in plasma and brain tissue were determined by liquid chromatography tandem mass spectrometry (LC–MS/MS) after intravenous administration of PGB or GB. After calculation and analysis, the drug-targeting index (DTI) of PGB was 7.45 and area under curve (AUC) value of GB decomposed from PGB was 2.45-fold higher than that of GB (parent drug) in brain. All the above results indicated that the brain targeting of GB was improved by prodrug strategy.  相似文献   

14.
羟基红花黄色素A对血小板活化因子的拮抗作用   总被引:64,自引:0,他引:64  
臧宝霞  金鸣  司南  张彦  吴伟  朴永哲 《药学学报》2002,37(9):696-699
目的观察羟基红花黄色素A(HSYA)对血小板活化因子(PAF)的拮抗作用.方法以放射受体结合试验观察HSYA抑制[3H]PAF与家兔洗涤血小板(WRP)特异性结合的作用,以比浊法观察HSYA抑制PAF介导的WRP及兔多型核白细胞(PMNs)聚集的作用.结果 HSYA可浓度依赖地抑制1,2及4 nmol·L-1 [3H]PAF与WRP受体的结合;HSYA抑制PAF介导的WRP及兔PMNs聚集,均具明显的量效关系,其IC50分别为0.99及0.70 mmol·L-1.结论 HSYA有PAF受体拮抗作用.  相似文献   

15.
Aglafoline, isolated from Aglaia elliptifolia Merr, inhibited in a selective and concentration-dependent manner the aggregation and ATP release reaction induced in washed rabbit platelets by PAF (platelet-activating factor). The IC50 values of aglafoline, BN52021 and kadsurenone on PAF (3.6 nM)-induced platelet aggregation were about 50, 12 and 18 microM, respectively. Aglafoline also inhibited [3H]PAF (3.6 nM) binding to washed rabbit platelets with an IC50 value of 17.8 +/- 2.6 microM. The concentration-response curve of PAF-induced platelet aggregation was shifted to the right by aglafoline with pA2 and pA10 values of 5.97 and 5.04, respectively. Although thromboxane B2 formation caused by collagen and thrombin was partially suppressed by aglafoline, thromboxane B2 formation caused by ionophore A23187 and arachidonic acid was not affected. Aglafoline inhibited the [3H]inositol monophosphate formation caused by PAF but not that caused by collagen or thrombin in the presence of indomethacin (20 microM). The cAMP content of washed rabbit platelets was not affected by aglafoline. Rat femoral intravenous administration of aglafoline (10 mg/kg) did not affect blood pressure. However, aglafoline (10 mg/kg) both prophylactically and therapeutically antagonized PAF (2.5 micrograms/kg)-induced hypotensive shock in rats. Intravenous PAF (30 ng/kg) caused severe bronchoconstriction in guinea pigs. This effect was completely blocked by aglafoline. This implies aglafoline is an effective PAF antagonist not only in vitro, but also in vivo.  相似文献   

16.
Shen Z  Dong Z  Cheng P  Li L  Chen Z  Liu J 《Planta medica》2003,69(7):605-609
The effects of plumbagin were investigated on platelet aggregation in vitro and ex vivo, on the binding of thrombin-stimulated platelets to neutrophils, and platelet aggregation induced by intact neutrophils and N-formyl-methionyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF) activated neutrophils, by use of the methods of Hamburger, McEver and Born, respectively. The results showed that plumbagin in vitro significantly inhibited adenosine diphosphate (ADP)-, arachidonic acid (AA)-, or platelet activating factor (PAF)-induced platelet aggregation, in a concentration-dependent manner. The medium inhibitory concentrations (IC 50 ) were 39.4, 82.7 and 38.1 microM, respectively. Intragastric plumbagin at 10 mg/kg markedly suppressed platelet aggregation induced by ADP, AA, or PAF. Plumbagin decreased the binding between thrombin-stimulated platelets and neutrophils with an IC 50 of 62.9 microM. Plumbagin significantly inhibited washed platelet aggregation stimulated by fMLP- or PAF-activated neutrophils. The IC 50 values were 54.3 and 47.6 microM, respectively. On the other hand, plumbagin and aspirin increased the inhibition of intact neutrophils on AA-induced platelet aggregation. It is suggested that plumbagin inhibited platelet aggregation in vitro and ex vivo, suppressed the binding of activated platelets to neutrophils, inhibited platelet aggregation induced by activated neutrophils, and increased inhibition of intact neutrophils on platelet reactivity. Abbreviations. DMSO:dimethyl sulphoxide fMLP: N-formyl-methionyl-leucyl-phenylalanine ADP:adenosine diphosphate AA:arachidonic acid PAF:platelet activating factor  相似文献   

17.
A novel class of 2-(4-heterocyclylphenyl)-1,4-dihydropyridines (2-38) possessing antagonist activity against platelet activating factor (PAF) was prepared by the Hantzsch synthesis from a variety of ethyl 4'-heterocyclic-substituted benzoylacetates, aryl or heteroaryl aldehydes, and substituted 3-aminocrotonamides or 3-aminocrotonate esters. Structure-activity relationships were evaluated where PAF antagonist activity was measured in vitro by determining the concentration of compound (IC50) required to inhibit the PAF-induced aggregation of rabbit washed platelets, and in vivo by determining the oral dose (ED50) which protected mice from a lethal injection of PAF. The nature of the substituent at the dihydropyridine 2-position was found to be important for both in vitro and in vivo activity, whereas there was greater flexibility for structural variation at the 4- and 5-positions. The most potent compound was 4-(2-chlorophenyl)-1,4-dihydro-3-(ethoxycarbonyl)-6-methyl-2-[4-(2- methylimidazo[4,5-c]pyrid-1-yl)phenyl]-5-[N-(2- pyridyl)carbamoyl]pyridine (17, UK-74,505), IC50 = 4.3 nM, ED50 = 0.26 mg/kg po, which was found to be approximately 33 times more potent in vitro (rabbit platelet aggregation) and about 8 times more potent in vivo (murine lethality) than WEB2086. Compound 17 also exhibited a long duration of action in the dog (inhibition of PAF-induced whole blood aggregation ex vivo was maintained for greater than 24 h following a single oral dose of 75 micrograms/kg) and was highly selective as a PAF antagonist, showing only weak affinity (IC50 = 6600 nM) for the [3H]nitrendipine binding site. As a result of its high oral potency, selectivity, and duration of action, UK-74,505 has been selected for clinical evaluation.  相似文献   

18.
The effects of dl-erythro-4-benzyl-alpha-(4-hydroxyphenyl)-beta-methyl-l-piperidine-eth anol tartrate (ifenprodil tartrate) on rabbit platelet aggregation in vitro and ex vivo were studied. Ifenprodil tartrate inhibited platelet aggregation in vitro induced by ADP, collagen and epinephrine. It also inhibited 5-hydroxytryptamine (5-HT) uptake into platelets and 5-HT release from platelets. Since these inhibitory effects of ifenprodil tartrate on the functions of rabbit platelets were similar to the effects of imipramine, the effects of ifenprodil tartrate may be due to the stabilizing action of ifenprodil tartrate on the platelet membrane. The platelet aggregation by ADP was significantly inhibited in rabbits after oral administration of ifenprodil tartrate, the maximal plasma level of ifenprodil being reached at 20 ng/ml ex vivo, while the maximal level was only 1/40 of the minimal concentration of ifenprodil tartrate necessary to inhibit platelet aggregation in vitro. These results indicate that factors other than ifenprodil tartrate acting directly on the platelets (e.g., PGI2 which is an endogenous inhibitor of platelet aggregation) are involved in inducing the inhibitory effects of ifenprodil tartrate on platelet aggregation ex vivo. The effects of ifenprodil tartrate on both PGI2 release from the aorta and the inhibitory effects of PGI2 on platelet aggregation in vitro were investigated: PGI2 was found to intensify the inhibitory effects of ifenprodil tartrate on platelet aggregation in vitro, but there was little effect, if any, on PGI2 release. Therefore, it is considered that the ex vivo effects of ifenprodil tartrate might be due to its interaction with endogenous PGI2 in the blood.  相似文献   

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