dl-四氢巴马汀对实验性脑血栓形成及体外血小板聚集的抑制作用

目的：观察ｄｌ－四氢巴马汀（ｄｌ－ＴＨＰ）对大鼠实验性脑血栓形成的影响。并观察体外ｄｌ－ＴＨＰ对二磷酸腺苷、花生四烯酸和胶原诱导的兔血小板聚集的影响。方法：采用经大鼠颈动脉顺行注射复合血栓诱导剂（二磷酸腺苷、凝血酶和肾上腺素）造成的脑血栓模型。结果：ｄｌ－ＴＨＰ（１５、７．５ｍｇ·ｋｇ－１）ｉｖ对大鼠实验性脑血栓形成有明显的抑制作用。ｄｌ－ＴＨＰ对二磷酸腺苷、花生四烯酸和胶原诱导的兔血小板聚集均有抑制作用，并呈剂量依赖关系。结论：其作用可能是通过拮抗钙离子的作用而产生。     

Inhibition of platelet aggregation by adenosine receptor agonists

2-(Ar)alkoxyadenosines, which are agonists selective for the A_2AAR in PC 12 cell and rat striatum membranes, are also agonists at the A₂AR coupled to adenylate cyclase (AC) that mediates the inhibition of platelet aggregation. A panel of twelve well-characterized adenosine analogues stimulated human platelet AC and inhibited ADP-induced platelet aggregation at sub- to low-micromolar concentrations with a potency ranking CGS 21680 < adenosine < R-PIA. There were significant correlations between the ECso of anti-aggregatory activity and either the ECso of stimulation of platelet and PC 12 cell AC (r ² = 0.66 and 0.67, respectively) or the K₁ of inhibition of [³H]NECA binding to the rat striatum membranes (r ² = 0.75). Likewise, platelet AC stimulation correlated well with stimulation of PC 12 cell AC and with [³H]NECA binding (r ² = 0.94 and 0.91, respectively). Ten 2-(ar)alkoxyadenosines stimulated platelet AC at EC₅₀s ranging between 0.16 and 2.3 μM and inhibited platelet aggregation at EC₅₀s ranging between 2 and 30 μM. There were no correlations between the EC₅₀s of anti-aggregatory activity and either the EC₅₀s of the stimulation of platelet or PC 12 AC (r ² = 0.08 and 0.06, respectively) or with the K₁ of the inhibition of [³H]NECA binding to the A_2aAR in rat striatum (r ² = 0.02). The EC₅₀s of the stimulation of platelet AC correlated with those of the stimulation of PC 12 AC (r ² = 0.48), and also with the K₁ of [³H]NECA binding (r ² = 0.71). Each of the 23 adenosines completely inhibited platelet aggregation and thus, functionally, all behaved as full agonists. As stimulants of PC 12 cell AC, Group A and B analogues were equally efficacious. As stimulants of platelet AC, however, the efficacy relative to NECA ( = 1.0) of Group B analogues was significantly less than that of Group A analogues, 0.49 ± 0.2 vs. 0.72 ± 0.05, P±0.01. The partial agonist activity of Group B analogues at the platelet A2AR but full agonist activity at the PC 12 cell A_2aAR, as well as the relatively low correlations between platelet AC stimulation and other indices of A_2aAR agonist actlVlty, suggest the platelet receptor is not a typical A_2aAR. Further, the lack of a correlation between the platelet anti-aggregatory and AC stimulatory activity suggests that (a) the 2-(ar)alkoxyadenosines might affect platelet aggregation by mechanisms other than AC stimulation or (b) that the stimulation of the platelet membrane AC by 2-(ar)alkoxy-adenosines does not correspond to the accumulation of cyclic AMP in intact platelets.     

Effects of adenosine derivatives on human and rabbit platelet aggregation

Summary The inhibitory effects of several adenosine analogues, including the new A2-selective agonists 2-[p-(2-carboxyethyl)phenethylamino]-5-N-ethylcarboxamido-adenosine (CGS 21680) and 2-hexynyl-5-N-ethylcarbox-amidoadenosine (2-hexynyl-NECA), were investigated in vitro on human and rabbit platelet aggregation. The compounds examined inhibited ADP-induced platelet aggregation over a wide range of potency. The rank order of activity was similar between the two species thus showing that the rabbit is a useful animal model for studying the effects of adenosine derivatives on platelet aggregation. 2-Hexynyl-NECA was found to be the most potent adenosine compound of those currently available, having IC₅₀ values of 0.10 and 0.07 M in human and rabbit platelets, respectively. Conversely, the A1 agonists R(–)-N-⁶-(2-phenylisopropyl) adenosine (R-PIA), S(+)-N⁶-(2phenylisopropyl) adenosine (S-PIA) and 2-chloro-N⁶-cyclopentyl-adenosine (CCPA) were the least potent compounds with IC₅₀ values in the micromolar range. The potency of the compounds in inhibiting platelet aggregation was found to be highly correlated with their affinity for A2 receptors as measured using 3H-CGS 21680 binding in rat brain striatum.Correspondence to S. Dionisotti at the above address     

Effects of selective dopamine receptor subtype agonists on cardiac contractility and regional haemodynamics in rats

1. Activation of dopamine (DA) receptors produces cardiovascular responses such as vasodilation and hypotension. However, knowledge of the role of specific dopamine receptor subtypes (especially D3 and D4) in the cardiovascular system is limited. The objective of the present study was to characterize the haemodynamic and cardiac responses to agonists with selectivity for D1, D2, D3 and D4 receptor subtypes. 2. Inactin-anaesthetized rats were instrumented to measure regional haemodynamic and cardiac contractility responses with slow intravenous infusion of agonists. 3. Fenoldopam (a D1 receptor agonist) decreased (P < 0.05) renal vascular resistance beginning at a dose of 3 micromol/kg. Infusion of PNU-95666E (a D2 receptor agonist) produced dose-dependent decreases (P < 0.05) in mean arterial pressure (MAP), heart rate (HR) and hindquarter vascular resistance (HQVR). Administration of BP897 (a partial D3 receptor agonist) decreased (P < 0.05) MAP and HQVR at 3 micromol/kg. PD168077 (a D4 receptor agonist) caused significant increases in HQVR at 1 micromol/kg. None of the compounds tested elicited significant changes in cardiac contractility. 4. Using selective agonists of dopamine receptor subtypes, the present studies characterize distinct cardiovascular effects in anaesthetized rats. Consistent with its well-defined effects as a D1 receptor agonist, fenoldopam administration resulted in renal vasodilation. Similar to earlier studies using the non-selective D2-like receptor agonist quinpirole, selective agonism at the D2 receptor using PNU-95666E resulted in bradycardia, hindquarter vasodilation and decreases in arterial pressure. Partial agonism at the D3 receptor with BP897 had no effect on heart rate, but did produce depressor responses driven by decreases in HQVR. Conversely, agonism of the D4 receptor using PD168077 resulted in modest hindquarter vasoconstriction that was not dose dependent. Hence, by comparison, agonism of the D4 receptor has little effect in the cardiovascular system of the rat relative to the other dopamine receptor subtype agonists tested.     

血栓弹力图评价阿司匹林与氯吡格雷对脑梗死患者血小板聚集功能的影响

目的：研究通过血栓弹力图（TEG）比较阿司匹林与氯吡格雷对血小板聚集功能的影响,探讨TEG 在脑梗死患者抗血小板药物个体化治疗中的意义。方法采用 TEG 检测100例急性脑梗死患者抗血小板药物治疗后花生四烯酸（AA）和腺苷二磷酸（ADP）受体途径诱导的血小板抑制率,患者抗血小板药物治疗包括阿司匹林组（n ＝50）、氯吡格雷组（n ＝50）。比较两组血小板抑制率、患者神经功能评分、卒中复发率。结果TEG 显示阿司匹林组的血小板抑制率为（85．23±21．98）％,显著高于氯吡格雷组的（47．31±22.37）％（t ＝7．340,P ＝0．005）;TEG 显示阿司匹林与氯吡格雷血小板抑制率为良好的患者,神经功能恢复更佳（P ＜0．05）,其中阿司匹林抑制率显示良好的患者1年内卒中复发率更低（χ2＝4．460,P ＝0．035;χ2＝7.232,P ＝0．007）。结论TEG 对脑梗死患者抗血小板个体化治疗具有指导作用,可用于监测药物疗效以及评估患者预后。     

Inhibition of human and rabbit platelet aggregation by chlorophenoxyacid herbicides

Inhibition of human platelet aggregation by eight chlorophenoxyacid herbicides was studied in vitro. Thrombocyte aggregation in the platelet-rich plasma was induced by 1.0–32.0 M adenosine diphosphate (ADP), 0.32–32.0 M adrenaline or 7.5–30.0 g/ml collagen with and without chlorophenoxyacid (0.05–2.0 mg/ml). Platelet aggregation by each inducer was inhibited dose dependently by all the eight chlorophenoxyacids at concentrations between 0.1 and 2.0 mg/ml. Increasing the concentrations of ADP and collagen but not of adrenaline inhibited the antiaggregatory action of chlorophenoxy-acids. No essential differences in inhibitory effect were found between different chlorophenoxyacids varying in respect of their ring substituents and the length of the carboxylic side chain. In the platelet-rich plasma prepared from rabbits 2.5 h after subcutaneous injection of 2,4-dichlorophenoxyacetic acid or 4-chloro-2-methylphenoxy-acetic acid (100–150 mg/kg), platelet aggregation by ADP was inhibited 20–30%, compared to plasma taken from the rabbits before the chlorophenoxyacid treatment. The inhibition had disappeared by 20–23 h after administration. The results indicate that chlorophenoxyacid herbicides inhibit human platelet aggregation. Furthermore, the inhibition is probably involved in haemorrhages known to occur in various tissues of animals intoxicated by chlorophenoxyacid herbicides.     

心脉康胶囊对家兔血小板聚集的影响

目的研究心脉康胶囊对二磷酸腺苷(ADP)、花生四烯酸(AA)、血小板活化因子(PAF)诱导兔血小板聚集的影响。方法采用Born法,检测不同条件下ADP、AA、PAF诱导的兔血小板聚集率。结果与空白对照组比较,2 g.kg-1心脉康胶囊组能显著抑制ADP、AA、PAF诱导的兔血小板聚集率(P<0.01),1 g.kg-1心脉康胶囊组能显著抑制ADP、PAF诱导的兔血小板聚集率(P<0.01)。结论心脉康胶囊能抑制兔血小板聚集率。     

普鲁卡因胺对小鼠肺栓塞和血小板MDA生成的影响

普鲁卡因胺对小鼠肺栓塞和血小板ＭＤＡ生成的影响庞建新，孙莉莎，王晓燕１，杨素琴，单春文（第一军医大学药理教研室，广州５１０５１５，中国）关键词普鲁卡因胺；血检形成；丙二醛；血小板聚集目的：探讨普鲁卡因胺（ＰＡ）对肺栓塞，血小板丙二醛（ＭＤＡ）及血小板...     

银杏总内酯抗血小板聚集与抗血栓作用

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.     

抗人血小板膜糖蛋白Ⅲa单克隆抗体抑制兔血栓形成的实验研究

目的　评价抗人血小板膜糖蛋白Ⅲa单克隆抗体SZ21抑制兔血栓形成的能力。方法不同浓度的SZ21（0、10及20μg／ml）分别加入兔富血小板血浆（PRP）中,进行二磷酸腺苷（ADP）诱导的兔血小板聚集试验;体内注射SZ21（1.5mg／kg）,注射前及注射后5、30及60分钟时制备兔PRP,分别进行聚集试验;用颈动静脉旁路血栓模型研究SZ21对兔血栓形成的作用,20只新西兰兔随机分成4组,体内注射SZ21,剂量为A组0.1mg／kg,B组0.4mg／kg,C组0.75mg／kg,D为对照组（SZ391mg／kg）,然后测定血栓重量。结果　体外20μg／ml的SZ21对兔血小板抑制率为80％;SZ21体内注射60分钟时完全抑制血小板聚集功能;血栓模型分组试验,各组平均栓重为A组31mg,B组21mg,C组20.2mg,D组31mg,B、C组与对照组间有明显统计学差异（P＜0.01）。结论　单克隆抗体SZ21能有效抑制兔动静脉旁路血栓形成。     

粉防己碱与牛磺酸合用对血小板聚集与血栓形成的影响

粉防己碱（Ｔｅｔ）和牛磺酸（Ｔａｕ）均能抑制ＡＤＰ、胶原和凝血酶诱导的大鼠血小板聚集及血栓形成。Ｔｅｔ抑制ＡＤＰ诱导聚集较强，Ｔａｕ则对胶原作用最明显，二药减半量合并应用时，较各药单用强     

Regulation of platelet function by catecholamines in the cerebral vasculature of the rabbit.

1. 111In-labelled platelets were monitored continuously in the cerebral and pulmonary vascular beds of anaesthetized rabbits. Dopamine can, depending upon the concentration, either potentiate or inhibit thrombin-induced platelet accumulation in the cerebral vasculature of rabbits by unknown mechanisms. The effects of specific adrenergic and dopaminergic receptor antagonists were tested upon dopamine's actions on intracarotid (i.c.) thrombin-induced (80 u kg-1) platelet accumulation in the cerebral vasculature. The effect of adrenaline on the response to thrombin in this vascular bed was also investigated. 2. Thrombin-induced platelet accumulation was significantly (P<0.01) potentiated by dopamine (100 microgkg-1 min-1, i.c.) and this effect was significantly inhibited by infusion of the alpha-adrenoceptor antagonist, phentolamine. 3 A higher dose of dopamine (2 mg kg-1 min-1, i.c.) inhibited thrombin-induced platelet accumulation. The beta-adrenoceptor antagonist, propranolol, did not significantly alter this inhibitory effect whereas it was abolished by the dopamine D1 selective antagonist, SCH23390. 4 Adrenaline (when administered i.c. by bolus injection or infusion) had no significant effect on thrombin-induced accumulation at any of the doses tested. 5 Potentiation of in vivo platelet accumulation by dopamine therefore seems to occur via alpha-adrenergic receptors. However, the inhibitory effect of dopamine appears to be exerted via the activation of dopamine D1 receptors and not via beta-adrenergic receptors. Our findings confirm that dopamine, but not adrenaline, can modify platelet function in the cerebral vasculature and these observations may have implications for current and potential therapeutic uses of dopamine and selective dopaminergic compounds.     

阿斯匹林、奥昔麻黄碱及两者并用对血小板聚集和血栓形成的影响

阿斯匹林与奥昔麻黄碱均抑制ＡＤＰ诱导的大鼠体内血小板聚集和实验性脑血栓形成．滞后电刺激大鼠颈动脉血栓形成时间．减少肾上腺素和胶原复合诱导剂静注所致小鼠肺血栓造成的死亡．剂量与效应相关．两者合用作用增强．     

Effects of dopamine agonists on neurones in the caudate nucleus and cerebral cortex of cats chronically treated with neuroleptics.

It has been postulated that chronic administration of neuroleptics, by blocking central dopamine receptors, interrupts dopaminergic transmission and thereby allows the development of supersensitivity at post-synaptic dopaminoceptive sites. In order to test this hypothesis, dopamine and two dopaminergic agents, apomorphine and piribedil, were tested microiontophoretically upon caudate and cortical neurones of cats chronically treated with chlorpromazine or haloperidol for 6 months.No significant differences in neuronal sensitivity to dopamine and dopaminergic agents were observed between normal and long-term neuroleptic-treated cats.     

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。     

粉防己碱对兔血小板聚集和血小板活化因子生成的影响(英文)

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.     

白藜芦醇对高脂血症大鼠血小板聚集的影响及其机制研究

目的:研究白藜芦醇对高脂血症大鼠血小板聚集的影响及其可能机制.方法:建立大鼠的高脂血症模型,同时连续i.g.给予白藜芦醇(50mg· kg-1·d-1)或空白溶媒30 d,测定大鼠血浆TC、TG、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙二醛(MDA)、超氧化物歧化酶(SOD)、NO、内皮一氧化氮合酶(eNOS)、p-选择蛋白、血栓烷B2 (TXB2)和6-酮-前列腺素F1α(6-Keto-PGF1α),ADP诱导的血小板5 min最大聚集率.结果:与高脂模型组比较,高脂饲料白藜芦醇组大鼠在连续i.g.给予白藜芦醇(50 mg·kg-1·d-1)30 d后,大鼠血浆TG、TC、LDL-C含量均下降,分别下降19％、31％、51％,HDL-C含量增加1.33倍;SOD和eNOS活力升高,NO和6-Keto-PGF1α含量增加,MDA、p-选择蛋白、TXB2含量降低,ADP诱导的血小板5 min最大聚集率降低.结论:白藜芦醇能有效降低血小板聚集,可能是通过降低血脂水平,防止脂质过氧化和保护内皮细胞完整,影响NO合成,维持血浆或组织中的TXA2和PGI2平衡及细胞内外的钙离子平衡等多环节来发挥作用.     

不稳定性心绞痛患者血浆内皮素与血小板聚集的关系

目的 :探讨不稳定性心绞痛 (UA)患者血浆内皮素 (ET)与血小板聚集 (PA)的关系。方法 :采取随机对比方法 ,用放免法和比浊法分别测定UA患者即刻、12小时、24小时、48小时、72小时、1周时内皮素与血小板聚集值。结果 :UA组与对照组比较 ,差异非常显著 ,P<0 01 ;ET与PA呈正相关 ,r=0.61,P<0 05。结论 :ET与PA异常是UA发生发展的重要因素 ,二者可能相互影响 ,促进血栓形成     

替格瑞洛对急性冠状动脉综合征患者血小板聚集的影响

目的比较替格瑞洛和氯吡格雷对急性冠状动脉综合征(ACS)患者血小板聚集的影响。方法 81例ACS患者被随机分为替格瑞洛组(A组,41例)和氯吡格雷组(B组,40例),比较两组服药前和服药后1、2、4、8、24h及治疗第7天的血小板最大聚集率(PMAR)、血小板聚集抑制率(IPA)及出血事件。结果两组服药前PMAR水平相近(P>0.05)。A组患者服药期间的PMAR均低于B组(P<0.01),IPA及IPA≥50%的患者比例均高于B组(P<0.01)。B组服药后2h的IPA低于服药后8h(P<0.01),而A组两个时间段IPA差异无统计学意义(P>0.05)。两组均只有轻微出血事件。结论在ACS患者,替格瑞洛较氯吡格雷更能有效地抑制血小板聚集;两药短期的安全性相仿。     

阿托伐他汀联合抗血小板药治疗对脑血栓临床效果、血小板参数及预后分析

目的探析阿托伐他汀与抗血小板药联合治疗脑血栓的临床果,同时对患者的血小板参数及预后情况展开研究.方法90例脑血栓患者,随机分为参照组和联合组,每组45例.参照组患者采取常规对症治疗,联合组患者在参照组基础上予以阿托伐他汀与抗血小板药物联合治疗.比较两组患临床疗效、治疗前后血小板参数(血小板计数、血小板粘附率以及平均血小板体积)及后遗症、脑血管事件复发情况.结果联合组的总有效率91.1%显著高于参照组的75.6%,差异具有统计学意义(P<0.05).治疗后,两组患者的血小板计数、血小板粘附率以及平均血小板体积水平均低于本组治疗前,且联合组显著低于参照组,差异均具有统计学意义(P<0.05).联合组后遗症发生率6.7%低于参照组的22.2%,差异有统计学意义(P<0.05).联合组脑血管事件复发率13.3%低于参照组的0,差异具有统计学意义(P<0.05).结论对脑血栓患者采取阿托伐他汀与抗血小板药物联合治疗,疗效明显,且可改善患者的血小板参数,减少后遗症发生率,值得在临床上推广与运用.