血浆LPO、TXA_2/PGI_2平衡与糖尿病微血管病变的关系

作者测定了50例正常人,94例糖尿病患者血浆过氧化脂(LPO)及血浆6—酮—前列腺素 F_1α(6—酮—PGF_1α)和血栓素 B_2(TXB_2)的浓度,并分析血浆 LPO、TXB_2/6—酮—PGF_1α比值与糖尿病微血管病变的关系。结果有微血管病变糖尿病患者血浆 LPO 显著高于无微血管病变糖尿病患者。有微血管病变糖尿病患者血浆 TXB_2/6—酮—PGF_1α比值显著高于对照组,无微血管病变糖尿病患者两者比值与对照组相比无显著差异。有微血管病变糖尿病患者血浆 LPO 与 TXB_2/6—酮—PGF_1α比值呈正相关。提示有微血管病变并发症的糖尿病患者存在血浆 LPO 升高和循环 TXA_2与前列环素 PGI_2的比例失衡.     

咪苯嗪酮对血小板聚集、血栓形成和血小板环磷酸腺苷含量的影响

本文观察了新型强心剂咪苯嗪酮(Cl-914)对血小板聚集、血栓形成和血小板cAMP含量的影响。用比浊法测定Cl-914体外抑制AA,ADP和胶原诱导兔血小板聚集的IC_(50),分别为2.6,8.9和15.8μM;大鼠iv Cl-914 1.25mg/kg能抑制实验性血栓形成,20 mg/kg能抑制上述三种诱导剂引起的血小板聚集。在体外,用竞争性蛋白结合法测定,CI-914可使洗涤兔血小板cAMP含量明显升高。CI-914能以剂量依赖方式协同PGE_1抑制血小板聚集和升高血小板cAMP的含量。提示CI-914升高血小板cAMP含量可能是其抑制血小板聚集和抗血栓形成的主要机理。     

益康唑和克霉唑对血小板聚集及TXB_2和PGE_2生成的影响

益康唑,克霉唑,咪康唑和酮康唑体外抑制AA诱导兔血小板聚集比抑制ADP诱导大鼠血小板聚集的作用强。其中益康唑和克霉唑抑制AA诱聚兔血小板的IC_(50)分别是6.4及11.6μmol/L。放射免疫法测定大鼠血小板产生的TXB_2及PGE_2发现益康唑和克霉唑在5～50 nmol/L浓度下,能抑制TXB_2产生,同时增加PGE_2生成量,并呈良好的剂量效应相关。浓度为0.1～100μmol/L时,TXB_2的生成仍被抑制,而PGE_2的生成量反而逐渐降低。两药对TXB_2生成的抑制作用比Daz强。     

肺心病患者血栓素A_2—前列环素平衡的研究

本文用放免法测定了29例肺心病患者血浆TXB_26—酮—PGF_1~α水平的变化,同时对其平均肺动脉压及血气进行了测定。结果表明:肺心病急性加重期TXB_2升高,6—酮—PGF_1~α下降,TXB_2/6—酮—PGF_1~α比值升高。缓解期,TXB_2下降,6—酮—PGF_1~α上升,TXB_2/6—酮—PGF_1~α下降,但均末达到正常水平。相关分析表明:ppA与TXB_2正相关,与6—酮—PGF_1~α负相关、与TXB_26—酮-PGF_1~α正相关;PaO_2与6—酮—PGF_1~α正相关与TXB_26-酮-PGF_1~α负相关。提示肺心病存在TXA_2-PGI_2平衡失调,且此平衡失调在低氧性肺血管收缩中起重要作用。     

绞股蓝提取物对家兔血小板聚集和花生四烯酸代谢的影响

绞股蓝提取物(0.25～2g/L,终浓度)在体外明显抑制花生四烯酸诱导的家兔血小板聚集和血栓素B_2(TXB_2)释放,剂量与效应相关;该药抑制血小板释放TXB_2的ID_(50)为0.28g/L。体内实验静脉注射绞股蓝提取物35mg/kg后10和20min时,血小板聚集明显抑制,10～40min期间血小板释放TXB_2量明显减少,以10和20min时最著。该药(0.25～4g/L)在体外对家兔胸主动脉释放6-酮-PGF_(1α)无影响。实验结果表明,绞股蓝提取物对降低血栓素A_2/前列环素比值有较好作用。     

非胰岛素依赖型糖尿病患者血浆LPO、TXB_2、6—酮—PGF_1α水平改变及临床意义

本文报告77例非胰岛素依赖型糖尿病(NIDDM)病人及50例正常对照者血浆过氧化脂(LPO)、血栓素B_2(TXB_2)与6—酮—前列腺素F_1α(6—酮—PGF_1α)及血脂等测定结果,发现糖尿病人血浆LPO、TXB_2水平增高,6—酮—PGF_1α水平降低,在并发血管病变组尤明显;结果提示血浆LPO升高、血栓素A_2(TXA_2)与前列环素(PGI_2)平衡失调在糖尿病血管病变发病上起一定作用,临床上纠正其失调对防治糖尿病血管病变可能有重要意义。     

6-(αα-二苯基乙酰哌嗪基苯基)-4,5-二氢-5-甲基-3(2H)-哒嗪酮对兔血小板聚集及TXB_2,cAMP的影响

6-(αα-二苯基乙酰哌嗪基苯基)-4,5-二氢-5-甲基-3(2H)-哒嗪酮(简称DMDP)是我院新合成的哒嗪酮的衍生物。DMDP可以显著抑制由花生四烯酸(AA(?),ADP和血小板活化因子(PAF)诱导的免血小板聚集,其IC_(50)分别为1.12±0.1.4.19±0.5和2.97±0.1μmol/L。实验还表明DMDP在1～500 μmol/L浓度范围内呈剂量依赖性地抑制兔血小板内血栓素B_2含量,但升高兔血小板内环腺苷酸水平,这可能是其抑制血小板聚集的作用机理之一。     

实验性急性心肌梗塞大鼠血和尿TXB_2、6-K-PGF_(1α)改变的初步观察

本文报道30只急性心梗大鼠心梗24小时血 TXB_2、6-K-PGF_(1α)、PRA 和 AT Ⅱ水平,以20只大鼠作对照。同时测定心梗大鼠梗塞前后24小时尿 TXB_2、6-K-PGF_(1α)浓度改变。其结果:心梗大鼠血 TXB_2、6-K-PGF_(1α)浓度较对照组明显升高(P<0.01)。心梗后24小时尿 TXB_2、6-K-PGF_(1α)及其肌肝矫正值较心梗前24小时显著升高(P<0.01),提示 TXA_2、PGI_2参与急性心梗的病理过程。相关分析未见血、尿 TXB_2、6-K-PGF_(1α)及其比值与大鼠尸检梗塞范围有相关性(P>0.05)。但发现心梗组血 PRA、AT Ⅱ较对照组显著升高(P<0.01)。     

6-(αα-二苯基乙酰哌嗪基苯基)-4,5-二氢-5-甲基-3(2H)-哒嗪酮对兔血小板聚集及TXB2,cAMP的影响

6-(αα-二苯基乙酰哌嗪基苯基)-4,5-二氢-5-甲基-3(2H)-哒嗪酮(简称DMDP)是我院新合成的哒嗪酮的衍生物。DMDP可以显著抑制由花生四烯酸(AA(?),ADP和血小板活化因子(PAF)诱导的免血小板聚集,其IC₅₀分别为1.12±0.1.4.19±0.5和2.97±0.1μmol/L。实验还表明DMDP在1～500 μmol/L浓度范围内呈剂量依赖性地抑制兔血小板内血栓素B₂含量,但升高兔血小板内环腺苷酸水平,这可能是其抑制血小板聚集的作用机理之一。     

蛇毒抗栓酶对冠心病、高血压病患者血浆血栓素和前列环素的影响

用蛇毒抗栓酶以自身对照方法治疗17例急性心肌梗塞、38例心绞痛和19例高血压病患者,分别测定不同治疗时间患者血浆TXB_2、6—酮—PGF_1α浓度。结果表明:用药后各组TXB_2和T/K比值均见下降,6—酮—PGF_1α逐渐升高。提示蛇毒抗栓酶有影响前列腺素代谢,调节TXA_2与PGI_2平衡的作用,该药抑制血小板聚集的作用与此有关。     

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。     

In vitro antiplatelet profiles of the new thromboxane synthetase inhibitor sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo[b]thiophene-6-carboxylate

The in vitro properties of CS-518 (RS-5186; sodium 2-(1-imidazolylmethyl)- 4,5-dihydrobenzo[b]thiophene-6-carboxylate, CAS 113817-57-5), a new thromboxane (TX) synthetase inhibitor, as an antiplatelet agent were investigated. Incubation of clotting whole blood from man, rabbits, and dogs with CS-518 resulted in a concentration-dependent reduction of TXB2 production and an increase in 6-keto-PGF1 alpha. Similar properties were also observed for ozagrel and isbogrel, but both agents were less effective on TXB2 production. CS-518 inhibited arachidonic acid (AA)- or collagen-induced platelet aggregation in platelet rich plasma (PRP) from man, rabbits and dogs. In addition, antiaggregatory effects of CS-518 were confirmed in whole blood by two methods: impedance method and free platelet count method. TXA2 formation in washed canine platelets in response to AA (0.1 mmol/l) was dose-dependently inhibited by incubation with CS-518. This inhibition by CS-518 was gradually attenuated after platelets were subsequently washed with drug-free buffer, but a dose-dependent inhibition was still observed with platelets that had been washed three times. Ozagrel also inhibited TXB2 formation when incubated with platelets, whereas this inhibition disappeared with platelets only washed once. In contrast, platelets treated with acetylsalicylic acid, an irreversible inhibitor of cyclooxygenase showed a comparable inhibition before and after they were washed three times. These results indicate that CS-518 exerts antiplatelet effects in vitro via potent, selective, and long-lasting but reversible inhibition on TX synthetase.     

Effects of CI-930, a novel phosphodiesterase III inhibitor, on platelet aggregation and arachidonic acid metabolism

In the platelet-rich plasma of rabbits, 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-5-methyl-3(2H)-pyridazinone (CI-930) inhibited platelet aggregation triggered by AA, U-46619, ADP, collagen and PAF, with the IC50 values of 0.91, 0.73, 2.12, 2.35 and 7.15 mumols/L, respectively. The inhibitory effect of CI-930 on AA-induced aggregation was potentiated by PGE1, an adenylate cyclase activator, and antagonized by SQ-22536, an adenylate cyclase inhibitor. The contents of cAMP in washed rabbit platelets were increased by CI-930 5-50 mumols/L. In the concentration range of 0.5-500 mumols/L, CI-930 reduced the synthesis of TXB2 by either washed rat or rabbit platelets or rat pleural neutrophils. At the same time, CI-930 induced a dose-dependent increase of PGE2, PGF2a, and PGD2 biosynthesis by rat platelets and had no significant influence on the formation of 6-keto-PGF1a by the neutrophils. It is showed that CI-930 is an anti-platelet agent with a wide-spectrum activity and its anti-aggregating action may be exerted by dual mechanisms, both increasing cAMP contents and selectively inhibiting TXA2 synthesis in platelets.     

去氢紫堇碱对兔血小板TXB2及主动脉6-keto-PGF1PGF1α含量的影响

Dehydrocorydaline (DHC) was shown to reduce the production of thromboxane B₂ (TXB₂)in platelets and 6-keto-prostaglandin F_1α (6-keto-PGF_1α in the aorta of rabbits in vitro. The effect of DHC increased with the increase of dose.DHC 0.41 mg was found to inhibit the formatiom of TXB₂ markedly while not reduce the content of 6-keto-FCF_1α. DHC also exhibited obvious inhibitory effect on the arachidonic acid (0.66mmol/L) induced formation of platelet malondialdehyde (MDA). These effects were similiar to the specific cycloxygenase inhibitor, aspirin (0.03 mg/ml). The results suggest that (1) DHC reduced both contents of TXA₂ and PGI₂ in vitro. (2) DHC markedly inhibited the system of cycloxygenase in cell microsomes. (3) As to whether TXA₂ synthetase or cycloxygenase was inhibited in these experiments is still to be elucidated.     

阿魏酸钠对花生四烯酸代谢的影响

利用放射薄层方法测定兔血小板花生四烯酸代谢产物TXB₂,PGE₂和PGF_2α。用放射免疫法测定兔血小板TXB₂及主动脉6-keto-PGF_1α。阿魏酸钠(SF,0.1～3.2 mmol/L),抑制¹⁴C-花生四烯酸转化为TXB₂,呈剂量效应关系,IC₅₀为0.762 mmol/L。SF在较高浓度(0.8～3.2mmol/L)时亦抑制PGE₂,PGF_2α的生成。用放免法观察到,SF对血小板TXB₂和动脉壁6-keto-PGF_1α的生成均有抑制作用,对TXB₂的作用较强。结果提示,SF可抑制兔血小板和动脉壁环氧酶活性。     

短毛五加总甙对血小板聚集和PGI_2/TXA_2平衡的影响(英文)

短毛五加总甙(AGVPS)是中药短毛五加(Acanthopanax gracilistylus var. pubescens)的有效成份。本文发现短毛五加总甙能抑制正常家兔由多种诱导因素所致的血小板聚集。同时,它还抑制花生四稀酸所致血小板聚集时TXA_2的产生,增加离体家兔胸主动脉PGI_2产生。在高脂喂养的动脉粥样硬化的家兔模型上,能提高血浆PGI_2水平。     

丁基苯酞对大鼠局灶性脑缺血和重灌后脑内TXB2和6—keto—PGF1α…

目的：观察丁基苯酞（ＮＢＰ）对大鼠局灶性脑缺血及重灌后海马，纹状体和皮层中ＴＸＢ２及６－ｋｅｔｏ－ＰＧＦ１α含量的影响，方法：尼龙线栓塞法造成大鼠局灶性脑缺血模型，ＴＸＢ２和６－ｋｅｔｏ－ＰＧＦ１α用放免法测定。结果：ＮＢＰ１０ｍｇ．ｋｇ＾－１治疗对缺血重灌注后脑组织中ＴＸＢ２的产生具有抑制作用，但对６－ｋｅｔｏ－ＰＧＦ１α的产生无明显作用，ＮＢＰ２０ｍｇ．ｋｇ＾－１治疗后，重灌５ｍｉｎ缺血脑组织     

2型糖尿病患者血浆血栓素B2与6-酮-前列腺素1α的变化及其临床意义

目的探讨2型糖尿病患者血浆血栓素B2（TXB2）、6-酮-前列腺素1α（6-keto—PGF1α）的变化及其在糖尿病大血管病变中的作用。方法采用放射免疫分析方法测定糖尿病组60例2型糖尿病患者（其中有大血管病变亚组43例,无大血管病变亚组17例）和31例对照组受试者的血浆TXB2、6-keto—PGF1α的浓度,并分析其相关性。结果血浆TXB2水平在糖尿病组有大血管病变亚组最高[（430．8±57．4）ng／L];糖尿病无大血管病变亚组次之[（237．2±92．6）ng／L];对照组最低[（80．8±33．8）．g／L]。血浆6-keto-PGF1α水平在糖尿病组有大血管病变亚组最低[（248．5±69．6）．g／L];无大血管病变亚组次之[（327．9±64．5）ng／L],对照组最高[（503．4±75．8）ng／L]。3组问分别进行方差齐性检验和两样本t检验,组间差异均具有统计学意义（均P〈0．05）。Pearson相关分析显示血浆TXB2与6-keto—PGF1α呈负相关（r=-0．829,P〈0．01）。结论TXB2、6-ke—to-PGF1α共同参与了2型糖尿病大血管病变的发生,可作为早期诊断和病情监测的指标。     

Effect of thromboxane A2 synthetase inhibition, singly and combined with thromboxane A2/prostaglandin endoperoxide receptor antagonism, on inositol phospholipid turnover and on 5-HT release by washed human platelets

Differential effects on human platelet function of thromboxane A2 (TXA2) synthetase inhibition singly and of TXA2 synthetase inhibition combined with TXA2/prostaglandin endoperoxide receptor antagonism were revealed, using ridogrel as a probe. Ridogrel combines selective TXA2 synthetase inhibition with TXA2/prostaglandin receptor antagonism in one molecule: in washed human platelets, the compound reduces the production of TXB2 (IC50 = 1.3 X 10(-8) M) and increases that of PGF2 alpha, PGE2, PGD2 from [14C]arachidonic acid. Additionally, at higher concentrations (Ki = 0.52 X 10(-6) M), it selectively antagonizes the breakdown of inositol phospholipids, subsequent to stimulation of TXA2/prostaglandin endoperoxide receptors with U 46619. The latter happens in a competitive way with fast receptor association-dissociation characteristics. At low concentrations (1 X 10(-9)-1 X 10(-7) M) producing single TXA2 synthetase inhibition, ridogrel reduces the collagen-induced formation of TXB2 by washed platelets, but enhances [32P]phosphatidic acid (PA) accumulation and [3H]5-hydroxytryptamine (5-HT) release. At higher concentrations (1 X 10(-6)-1 X 10(-5) M) which additionally block U 46619-induced [32P]PA accumulation, ridogrel inhibits the [32P]PA accumulation and release of [3H]5-HT by human platelets stimulated with collagen. These observations, corroborated by results obtained with OKY 1581, sulotroban, indomethacin and human serum albumin, suggest a causal role for prostaglandin endoperoxides in the stimulation by TXA2 synthetase inhibition of platelet reactions to collagen. They reinforce the concept that TXA2 synthetase inhibition-induced reorientation of cyclic endoperoxide metabolism, away from TXA2 into inhibitory prostanoids, requires additional TXA2/prostaglandin endoperoxide receptor antagonism to achieve optimal anti-platelet effects.