Effects of dl-3-n-butylphthalide on production of TXB_2 and 6-keto-PGF_(1α) in rat brain during focal cerebral ischemia and reperfusion

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缺血脑组织中ＴＸＢ２和重灌后３０ｍｉｎ时６ｋｅｔｏＰＧＦ１α含量皆明显减少．ＮＢＰ２０或１０ｍｇ·ｋｇ－１皆明显提高ＰＧＩ２／ＴＸＡ２的比值．而阿司匹林（２０ｍｇ·ｋｇ－１）除重灌５ｍｉｎ提高纹状体ＰＧＩ２／ＴＸＡ２的比值外，在其它时间点上均无提高作用．结论：ＮＢＰ提高缺血脑组织中ＰＧＩ２／ＴＸＡ２的比值，可能有利于改善缺血脑组织的微循环状态．     

Inhibitory effects of nimodipine on platelet aggregation and thrombosis

目的：研究尼莫地平（Ｎｉｍ）对大鼠体内血小板聚集和动脉血栓形成的影响．方法：比浊法测定血小板的聚集率和抑制率；电刺激法测定Ｎｉｍ对体内动脉血栓形成的影响，放免法测定Ｎｉｍ对血浆６酮前列腺素Ｆ１α和血栓素Ｂ２（６ｋｅｔｏＰＧＦ１α／ＴＸＢ２）含量的影响．结果：Ｎｉｍ４５，９，１８和３６ｍｇ·ｋｇ－１·ｄ－１ｉｇ４ｄ可显著抑制血小板的聚集．ＩＣ５０（９５％可信限）为２６（９－４４）ｍｇ·ｋｇ－１．Ｎｉｍ４５，９，１８ｍｇ·ｋｇ－１·ｄ－１ｉｇ４ｄ可显著延长电刺激诱导的颈动脉血栓形成时间．Ｎｉｍ９和１８ｍｇ·ｋｇ－１可明显改善血浆中６ｋｅｔｏＰＧＦ１α／ＴＸＢ２的比值．结论：Ｎｉｍ抗血栓作用部分与改善６ｋｅｔｏＰＧＦ１α／ＴＸＢ２比值有关．     

孕鼠血浆一氧化氮减少与内皮素、血栓素、前列环素的关系

本文研究一氧化氮减少对孕鼠血浆内皮素（ＥＴ）、血栓素Ｂ２（ＴＸＢ２）、６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）等血管活性因子的影响。结果显示妊娠大鼠血浆ＥＴ、ＴＸＢ２、６－ｋｅｔｏ－ＰＧＦ１α均升高，ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值降低，未妊娠大鼠血浆ＥＴ升高，６－ｋｅｔｏ－ＰＧＦ１α降低，ＴＸＢ２无显著变化，ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α比值升高。说明孕鼠体内一氧化氮减少时，ＥＴ及ＴＸＢ２上升，血管收缩，而作为代偿和保护机制，６－ｋｅｔｏ－ＰＧＦ１α升高，ＴＸＢ２比值降低。未妊娠大鼠无此代偿效应。     

尼莫地平对血小板聚集和血栓形成的抑制作用

目的：研究尼莫地平（Ｎｉｍ）对大鼠体内血小板聚集和动脉血栓形成的影响。方法：比浊法测定血小板的聚集率的抑制率；电刺激法测定Ｎｉｍ对体内动脉血栓形成的影响，放免法测定Ｎｉｍ对血浆６－酮前列腺素Ｆ１α和血栓素Ｂ２（６－ｋｅｔｏ－ＰＧＦ１α／ＴＸＢ２）ｍｇ·ｋｇ＾－１·ｄ＾－１ ｉｇ４ｄ可显著抑制血小板的聚集。ＩＣ５０（９５％）可信限）为２６（９－４４）ｍｇ·ｋｇ＾－１．Ｎｉｍ４．５，９，１８ｍｇ·ｋｇ     

芦丁复合物对兔实验性脑梗塞血浆中TXB2,6—Keto—PGF1α的影响

通过建立兔大脑中动脉阻塞局灶性脑缺血实验模型，测定缺血后及经芦丁复合物治疗后血浆中ＴＸＢ２、６－Ｋｅｔｏ－ＰＧＦ１α含量。结果发现ＴＸＢ２在脑梗塞后明显增高，而６－Ｋｅｔｏ－ＰＧＦ１α含量降低，经芦丁复合物治疗后ＴＸＢ２减少，６－Ｋｅｔｏ－ＰＧＦ１α增高，与缺血组比较有显著性差异（Ｐ〈０．０１）。提示芦丁复合物有明显的调节ＴＸＢ２／６－Ｋｅｔｏ－ＰＧＦ１α增高，与缺血组比较有显著性差异（Ｐ〈０．０     

Inhibitory Effect of β-Elemene Emulsion on Platelet Aggregation and its Mechanism

为阐明β榄香烯的抗血小板作用，本文分别采用比浊法和放免法测定大鼠连续ｉｐ７ｄβ榄香烯乳６．２５～１２．５ｍｇ·ｋｇ－１·ｄ－１后对血小板聚集、血浆ｋｅｔｏＰＧＦ１α和ＴＸＢ２水平的影响。结果表明，本品分别使凝血酶、花生四烯酸和ＡＤＰ诱导血小板最大聚集率下降３８．３％～４２．６％，１４．７％～１９．１％和７．２％～１０．８％，血浆ＴＸＢ２从８８ｎｇ·Ｌ－１下降至７２ｎｇ·Ｌ－１，ｋｅｔｏＰＧＦ１α从１７．５ｎｇ·Ｌ－１增加至２０．９ｎｇ·Ｌ－１。提示ＴＸＢ２降低和ｋｅｔｏＰＧＦ１α值增加是其抑制血小板聚集的作用机制之一。     

阿司匹林与尼莫地平合用大鼠颈动脉血栓形成的影响

目的：观察阿司匹林与尼莫地平合用对血栓形成的影响。方法：电刺激法形成大鼠颈动脉血栓,放免法栓测血浆凝血恶烷Ｂ２（ＴＸＢ２）和６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ－ＰＧＦ１α）含量。结果：合用后动脉血流阻塞时间显著延长,Ｑ值均大于１,且合用后血浆６－ｋｅｔｏ－ＰＧＦ１α／ＴＸＢ２比值也显著增加。结论：阿司匹林与尼莫地平可协同抑制动脉血栓形成。     

丁基苯酞对原代培养的大鼠皮层神经细胞外液6-keto-PGF_(1α)和TXB_2及其比值的影响

目的旨在观察丁基苯酞（ＮＢＰ）对神经细胞培养液中６酮ＰＧＦ１α和ＴＸＢ２含量及其比值的影响。用放射免疫方法，结果发现神经细胞在低糖低氧５ｈ或低糖低氧５ｈ／恢复糖氧３ｈ条件下，ｄ，ｌ和ｄｌＮＢＰ（０１～１００μｍｏｌ·Ｌ－１）能够剂量依赖性升高细胞外液中的６酮ＰＧＦ１α含量，降低ＴＸＢ２水平，从而使６酮ＰＧＦ１α与ＴＸＢ２比值升高。而阿司匹林仅在小剂量（０１，１μｍｏｌ·Ｌ－１）时能升高６酮ＰＧＦ１α与ＴＸＢ２比值，大剂量（１０，１００μｍｏｌ·Ｌ－１）时无影响。提示：ＮＢＰ对６酮ＰＧＦ１α／ＴＸＢ２比值的升高可能与其增加局部脑血流和改善缺血性脑损伤有关。     

芦丁复合物对兔实验性脑梗塞血浆中TXB_2、6－Keto－PGF_（1α）的影响

通过建立兔大脑中动脉阻塞局灶性脑缺血实验模型，测定缺血后及经芦丁复合物治疗后血浆中ＴＸＢ_２、６－Ｋｅｔｏ－ＰＧＦ_（１α）含量。结果发现ＴＸＢ_２在脑梗塞后明显增高，而６－Ｋｅｔｏ－ＰＧＦ_（１α）含量降低，经芦丁复合物治疗后ＴＸＢ_２减少，６－Ｋｅｔｏ－ＰＧＦ_（１α）增高，与缺血组比较有显著性差异（Ｐ＜０．０ｌ）。提示芦丁复合物有明显的调节ＴＸＢ_２／６－Ｋｅｔｏ－ＴＧＦ_（１α）平衡，减轻缺血性脑损伤的作用。     

阿司匹林与尼莫地平合用对大鼠颈动脉血栓形成的影响

目的：观察阿司匹林与尼莫地平合用对血栓形成的影响。方法：电刺激法形成大鼠颈动脉血栓,放免法栓测血浆凝血烷Ｂ２（ＴＸＢ２）和６＿酮＿前列腺素Ｆ１α（６＿ｋｅｔｏ＿ＰＧＦ１α）含量。结果：合用后动脉血流阻塞时间显著延长,Ｑ值均大于１,且合用后血浆６＿ｋｅｔｏ＿ＰＧＦ１α／ＴＸＢ２比值也显著增加。结论：阿司匹林与尼莫地平可协同抑制动脉血栓形成     

Roles of endogenous prostacyclin and thromboxane A2 in the ischemic canine heart

The ability of the ischemic heart to release prostacyclin (PGI2) and thromboxane A2 (TXA2) was studied, together with the effects of these substances on the ischemic myocardium in open-chest dogs. We measured the plasma levels of 6-keto-PGF1 alpha and TXB2--which are stable metabolites of PGI2 and TXA2, respectively--as well as lactate and coronary venous blood flow. The dogs were divided into three groups of eight animals which received indomethacin (5 mg/kg), (E)-3-[4-l-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046) (1 mg/kg), or the vehicle. A transient increase in 6-keto-PGF1 alpha was observed in the great cardiac vein 5 min after the ligation of the left anterior descending coronary artery (LAD). TXB2 and lactate increased 30 and 15 min, respectively, after the ligation. Indomethacin prevented significant increases in 6-keto-PGF1 alpha and TXB2, but accelerated the lactate release. OKY-046 prevented significant increases in TXB2 and lactate release, but did not counteract the increase in 6-keto-PGF1 alpha. Although coronary venous flow decreased significantly 5 min after the ligation in every group, the flow returned to the preligation level 15 min after the ligation in the OKY-046 and the vehicle groups. Thus, we have demonstrated the release of PGI2 and TXA2 from the ischemic heart and suggest beneficial effects of PGI2 and of a selective inhibitor of thromboxane synthetase on the ischemic myocardium.     

丹参酮Ⅱ-A对局灶性脑缺血大鼠COX-2、PGI2以及TXA2含量的影响

目的探讨丹参酮Ⅱ-A对局灶性脑缺血大鼠脑组织环氧化酶2(COX-2)及其下游产物含量的影响。方法 46只SD大鼠随机分为假手术(S)组(n=10)、缺血模型(I)组(n=11)和丹参酮Ⅱ-A低(T1)(n=12,丹参酮Ⅱ-A腹腔预注射1周,每日2mg/kg)、高(T2)(n=13,丹参酮Ⅱ-A腹腔预注射1周,每日4mg/kg)剂量预防组。采用持续性大脑中动脉线栓法制作局灶性脑缺血模型。持续栓塞3h后进行神经行为学评分,6h后断头取脑,干湿重法求出脑组织含水量,ELISA法测定脑组织中COX-2、6-酮前列腺素F1α(6-keto-PGF1α)、血栓素B2(TXB2)含量。结果与I组相比,T1、T2组神经功能损伤改善,脑组织含水量减少,COX-2、6-keto-PGF1α和TXB2的产生呈剂量依赖性的降低(P<0.01)。结论抑制COX-2及其下游产物TXA2、前列环素(PGI2)可能是丹参酮Ⅱ-A保护局灶性脑缺血大鼠神经功能的作用机制之一。     

氟比洛芬酯对大鼠脑缺血再灌注损伤后血浆血栓素A2和前列环素I2水平的影响

目的探讨非选择性环氧化酶抑制剂氟比洛芬酯对大鼠局灶性脑缺血再灌注损伤后血浆血栓素A2（TXA2）和前列环素12（Pcll2）水平的影响。方法采用线栓法建立大鼠大脑中动脉闭塞2h／再灌注24h动物模型。24只舍SD大鼠随机分成4组,每组6只：假手术组、生理盐水对照组、氟比洛芬酯6和12nlg·lcgll组。于插入线栓前10min分别给予2mL生理盐水、氟比洛芬酯6和12mg·kg^-1。大脑中动脉闭塞2I∥再灌注24h后采集大鼠血浆标本,放射免疫法检测血浆TXA2的代谢产物血栓素B2（ax~h）和PGl2的代谢产物6一酮一前列腺素1。（6-keto-PGF1a）浓度。结果大脑中动脉闭塞2l∥再灌注24h后对照组与假手术组相比,TX赐浓度显著增加[（1038．12-t-110．02）ng·L0V8（341．29±47．98）ng·L～,P〈0．01],6-keto-PC_．F1。显著减少[（539．79±45．07）ng·L-1VS（1268．24±131．01）ng·L_。,P〈O．01]。氟比洛芬酯6及12mg·kg^-1组与对照组相比能显著降低血浆’ⅨB2浓度[（605．534-45．27）、（495．46±66．03）rIg·L～,P〈0．01],增加血浆6-keto-I~,F1。浓度[（839．34±60．22）、（963．08±82．86）ng·L～,P〈0．01]。氟比洛芬酯12IIlg·kg^-l比6nag·kgll效果更为显著。结论氟比洛芬酯能减轻大鼠脑缺血再灌注损伤后血浆TXA2和PGl2的变化。     

Routine measurement of thromboxane B2 and the prostacyclin metabolite 6-keto-prostaglandin F1 alpha in plasma

Thromboxane A2 (TXA2) is mainly formed in thrombocytes. It promotes thrombocyte aggregation and contracts the blood vessels. TXA2 appears to be a specific physiological thrombotic agent. Synthesis of TXA2 is elevated in patients with diabetes mellitus of types I and II and in hypertensive patients. TXA2 has a half-life of about 30 s under physiological conditions. Prostacyclin (PGI2) is formed in the vessel walls. Its action is antagonistic to TXA2, that is, it inhibits platelet aggregation and dilates the blood vessels. Synthesis of PGI2 is depressed in the presence of the classical 4 main risk factors for atherosclerosis: arterial hypertension, hyperlipoproteinaemia, smoking and diabetes mellitus. PGI2 has a half-life of about 3 min under physiological conditions. Since TXA2 and PGI2 are very labile and thus extremely difficult to measure, it is at present usual to measure their stable metabolites thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Radioimmunological measurement (RIA) of TXB2 in plasma requires no preliminary work, but radioimmunological measurement of 6-keto-PGF1 alpha in plasma requires prior extraction and concentrating, since the concentration of 6-keto-PGF1 alpha in the plasma is usually below the detection limit of commercial RIA kits. This paper describes standardized conditions for drawing the blood sample, a simple method of extraction from plasma, and the reliability of two commercial RIA kits with 125I tracer in measuring TXB2 and 6-keto-PGF1 alpha in plasma.     

Protective effect of a novel thromboxane synthetase inhibitor, CV-4151, on myocardial damage due to coronary occlusion and reperfusion in the hearts of anesthetized dogs

The protective effect of a novel thromboxane (TX) synthetase inhibitor, (E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (CV-4151), on myocardial damage due to an ischemic episode and reperfusion was investigated in anesthetized, open-chested dogs. The left anterior descending coronary artery (LAD) was occluded for 60 min and subsequently reperfused for 60 min. CV-4151 was infused i.v. at a dose of 1 mg/kg over a 10-min period starting 20 min before the LAD occlusion. The agent had no acute hemodynamic effects. Within 30 min after LAD occlusion, 15.6-33.3% of dogs experienced ventricular fibrillation (VF); CV-4151 had no significant effect on the incidence of VF. After reperfusion, the frequency of ventricular extrasystoles (PVCs) was markedly increased, and 33.3% (9 of 27 dogs) died of VF in the control group. CV-4151 suppressed the exaggerated PVCs, and the incidence of VF in the group was 0% (0/18, p less than 0.05). Myocardial infarct size determined 60 min after reperfusion by a p-nitroblue tetrazolium (p-NBT) staining technique was significantly reduced by CV-4151. Increase in TXB2 release into the great coronary vein during reperfusion was completely inhibited by CV-4151, whereas release of 6-keto-PGF1 alpha tended to increase during occlusion and reperfusion. Thus, the ratio of 6-keto-PGF1 alpha to TXB2 levels was significantly increased throughout occlusion and reperfusion periods. These results suggest that inhibition of TXA2 synthesis is beneficial for protection of the myocardium during reperfusion from ischemic damage.     

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.