甘糖酯对家兔凝血和纤溶功能的影响

实验研究表明甘糖酯能够影响家兔凝血和纤溶功能。静脉注射6.25mg/kg,25mg/kg甘糖酯能明显延长家兔凝血酶原时间(PT)(P<0.001),凝血酶时间(TT)及白陶土部分凝血活酶时间(KPTT)(P<0.001),使家兔纤维蛋白原降解产物(FDP)明显增多(P<0.001),优球蛋白溶解时间(ELT)缩短(P<0.001),血浆纤维蛋白原含量(Fg)降低(P<0.05)。     

单甘酯对血小板功能及纤维蛋白原含量的影响

目的 :研究单甘酯对血小板聚集、粘附功能及出血时间和纤维蛋白原含量的影响。方法 :比浊法观察血小板聚集功能 ,玻瓶法观察血小板粘附功能 ,小鼠剪尾法观察出血时间 ,比色法测定纤维蛋白原含量。结果 :单甘酯 2 5、5 0mg/kg对血小板粘附有明显抑制作用 ,2 5、5 0、10 0mg/kg(iv)能明显抑制胶原和花生四烯酸诱导的血小板聚集 ,对ADP诱导的血小板聚集无抑制作用 ;40、80mg/kg(ip)可明显延长小鼠尾出血时间 ;2 5mg/kg(iv)即可降低大鼠血浆纤维蛋白原含量。结论 :单甘酯有明显的抑制血小板功能和降低血浆蛋白原含量的作用。     

甘糖酯对糖尿病大鼠血浆,肾脏内皮素和一氧化氮水平的影响

研究了甘糖酯对糖尿病大鼠血浆内皮素(ET)、一氧化氮(NO)水平、尿ET排泄量和肾皮质NO水平的影响。用链脲佐菌素引起大鼠糖尿病后3d,用甘糖酯(100mg/kg体重)处理3w。研究结果表明,糖尿病大鼠血浆ET、肾皮质NO水平和尿ET排泄量较对照组明显升高,血浆NO水平明显降低。甘糖酯处理的糖尿病大鼠血浆ET、肾皮质NO水平和尿ET排泄量较未处理的糖尿病动物明显下降,但未见对血浆NO水平有明显影响。这些结果表明,甘糖酯可影响糖尿病状态下ET和NO的合成和/或释放,提示甘糖酯减轻糖尿病肾脏病变部分是通过调节ET和NO的水平实现的。     

甘糖酯对鹌鹑实验性动脉粥样硬化预防作用的研究

甘糖酯(Propylene Glycol MannitaseSulfate),简称 PGMS 是一种新型类肝素海洋药物。本文研究甘糖酯对实验性动脉粥样硬化的预防作用。雄性朝鲜鹌鹑,喂饲高脂饲料加甘糖酯50或25mg/(kg·d)灌胃。测定实验前及开     

甘糖酯抗血栓作用及其机理研究

家兔iv甘糖酯6.25mg·kg~(-1)和25m g·kg~(-1)观察其对实验性血栓形成的影响.并与等抗凝效价藻酸双酯钠及肝素做比较,提示甘糖酯具有较好的抗血栓作用、为探讨其作用机理。本实验观察了甘糖酯对家兔抗凝血酶Ⅲ(AT—Ⅲ)及纤溶酶原活性的影响。发现甘糖酯可明显提高AT一Ⅲ功能活性,并使纤溶酶原活性升高;提示甘糖酯可通过抑制凝血系统和激活纤维蛋白溶解系统发挥其抗血栓作用。     

刺五加茎时对血小板聚集功能的影响

刺五加茎叶的乙醇提取液相当于生药量25～70mg/ml,体外实验能明显地抑制ADP、胶原所诱导的家兔血小板聚集。家兔iv 700mg/kg,10min后明显抑制ADP诱导的家兔血小板聚集,大白鼠iv 1000mg/kg,30min后明显抑制ADP诱导的血小板聚集。体外实验可使家兔血浆复钙时间明显延长。     

甘糖酯抗内皮细胞损伤的研究

研究甘糖酯对Ｅｃｏｌｉ内毒素和同型半胱氨酸所致鹌鹑血管内皮损伤的保护作用。结果表明：甘糖酯能显著降低血管内皮通透性，升高血浆６－酮－ＰＧＦ１ａ含量，降低管壁脂质过氧化物代谢产物ＭＤＡ含量，且药效同给药剂量成正相关，说明甘糖酯有抗内皮损伤作用。     

瑞香素抗血栓作用

瑞香素80 mg/kg iv对大鼠实验性血栓形成有明显的抑制作用,抑制率54%,在试管内当浓度为0.025,0.05及0.1 mg/ml时,可抑制ADP诱导的家兔血小板聚集。iv 80 mg/kg 5 min,对ADP诱导的家兔血小板聚集也有明显的抑制作用。iv 40及80 mg/kg 20 min,皆可使血小板粘附性降低;并能延长小鼠凝血时间。iv 80 mg/kg 5 min,对家兔纤维蛋白原含量,全血粘度及血浆比粘度均无明显影响。     

瑞香素抗血栓作用

瑞香素80 mg/kg iv对大鼠实验性血栓形成有明显的抑制作用,抑制率54%,在试管内当浓度为0.025,0.05及0.1 mg/ml时,可抑制ADP诱导的家兔血小板聚集。iv 80 mg/kg 5 min,对ADP诱导的家兔血小板聚集也有明显的抑制作用。iv 40及80 mg/kg 20 min,皆可使血小板粘附性降低;并能延长小鼠凝血时间。iv 80 mg/kg 5 min,对家兔纤维蛋白原含量,全血粘度及血浆比粘度均无明显影响。     

甘糖酯联合依折麦布对冠心病调脂疗效和安全性的临床观察

目的观察甘糖酯联合依折麦布对冠心病的调脂疗效和安全性。方法选择冠心病伴高脂血症患者共88例,随机分为甘糖酯组44例(给予甘糖酯100mg/次,3次/d),联合治疗组44例(给予甘糖酯片100mg/次,3次/d,依折麦布10mg/d)。观察2组治疗前后血脂水平、药物不良反应等。结果甘糖酯组和联合治疗组治疗8周末与治疗前比较,TC、TG、LDL-C、OX-LDL、CRP水平可见明显下降,HDL-C水平则明显升高,差异有统计学意义(P<0.05)。联合治疗组较甘糖酯组变化更显著,差异有统计学意义(P<0.05)。结论甘糖酯联合依折麦布可以显著降低冠心病伴高脂血症的血脂水平,优于单用甘糖酯,且安全性良...     

红景天甙元的药理研究

红景天甙元腹腔注射100mg/kg和200mg/kg对戊巴比妥钠入睡时间和催眠作用时间均无明显影响,300mg/kg可显著缩短戊巴比妥钠入睡时间和延长催眠作用时间,对电惊厥无保护作用,对常压缺氧所致动物死亡时间无明显影响,对高温所致动物死亡数无明显影响,对角叉菜胶所致踝关节肿胀有抑制作用,但局部用药对巴豆油所致耳部肿胀无抑制作用。红景天甙元给家兔静脉注射60mg/kg和150mg/kg,给大鼠腹腔注射200mg/kg,对胆汁排泌均无明显影响。离体实验,红景天甙元12.5×10~(-1)mg/ml可使大鼠离体回肠平滑肌张力降低,收缩幅度变小;25×10~(-1)mg/ml对Ach和BaCl_2引起的回肠平滑肌收缩均有抑制作用。     

Effects of Levcromakalim and RP52891 on NANCe Nerve-mediated Changes in Pulmonary Dynamics Evoked by Vagal Stimulation in the Guinea-pig

Summary: The effects of the potassium channel activators (KCA) levcromakalim and RP52891 on NANCe nerve-mediated changes in pulmonary dynamics were investigated in the anaesthetized guinea-pig, using a newly-developed respiratory dynamics computer. Levcromakalim (0.025-0.2 mg/kg iv) and RP52891 (0.05-0.5 mg/kg iv) caused dose-dependent inhibition of NANCe nerve-mediated increases in airways resistance (RAW) and decreases in dynamic compliance (C_dyn). These effects of the KCAs persisted for at least 1 h. Unlike NANCe nerve-mediated responses, equivalent challenges with exogenously-administered substance P (SP; 10-25 μg/kg iv) and neurokinin A (NKA; 0.5-2.0 μg/kg iv) tended to produce progressively increasing responses but this effect was not statistically significant. Levcromakalim (0.2 mg/kg iv) and RP52891 (0.5 mg/kg iv) did not significantly decrease responses to exogenously-administered SP, although NKA-induced bronchoconstriction was attenuated. Glibenclamide (25 mg/kg iv) partially reversed the NANCe-inhibitory effects of levcromakalim (0.1 mg/kg iv) and RP52891 (0.25 mg/kg iv) and fully reversed their hypotensive effects. We have shown that levcromakalim and RP52891 inhibit bronchoconstrictor responses to NANCe nerve stimulation. This involves the opening of a glibenclamide-sensitive K⁺-channel and may represent effects at a pre-junctional site on NANCe neurones to reduce transmitter release.     

Intravenous injection of flunarizine elicits epileptiform convulsions. Preliminary evaluation of anti-epileptic drugs

The possibility to elicit convulsions in rabbits after flunarizine, iv was investigated. A flunarizine solution, 3.3 mg/ml, was given iv at a rate of 1.5 ml/min in three fractional doses every 30 min. Action of anti-epileptic drugs in seizures induced by flunarizine was additionally examined. Convulsive seizures occurred 2-10 min after the last successive dose of flunarizine as alternating clonic and tonic seizures. A treatment with anti-epileptic drugs showed that both phenobarbital at doses 6, 7 and 7.5 mg/kg iv and pentobarbital at doses of 15, 20 and 25 mg/kg, iv did not entirely suppress convulsive seizures, although convulsive episodes were rare. Diazepam at doses of 1-1.5 mg/kg, iv suppressed convulsive seizures.     

The pharmacokinetics of 1,2-diethyl-3-hydroxypyridin-4-one (CP94) in rats.

The pharmacokinetics of 1,2-diethyl-3-hydroxypyridin-4-one (CP94) and its 2-(1-hydroxyethyl) metabolite (metabolite A) were examined in male Wistar rats using a chronically cannulated conscious-rat model. Serial blood samples were assayed by a reversed phase HPLC method with UV detection. Following iv doses of 25, 50, and 100 mg/kg, the parent compound was eliminated from blood in a biexponential fashion with an average systemic clearance of 1.5 liters/hr/kg. The mean terminal elimination half-life was 2.02 hr and the mean volume of distribution at steady state was 2.69 liters/kg. The areas under the curve (AUCs) for the 25, 50, and 100 mg/kg iv doses were 15, 36, and 72 micrograms/ml/hr, respectively, suggesting that the disposition of CP94 in rats obeys linear kinetics. The oral bioavailability of CP94 (100 mg/kg) was about 53%. Peak blood concentration occurred at about 0.5 hr after oral administration. Following iv doses of CP94 at 25, 50, and 100 mg/kg, metabolite A peaked at about 0.75 hr.     

Pentoxifylline attenuates bacterial lipopolysaccharide-induced enhancement of allyl alcohol hepatotoxicity.

Small amounts of exogenous lipopolysaccharide (LPS) (10 ng/kg-100 microg/kg) enhance the hepatotoxicity of allyl alcohol in male Sprague-Dawley rats. This augmentation of allyl alcohol hepatotoxicity appears to be linked to Kupffer cell function, but the mechanism of Kupffer cell involvement is unknown. Since Kupffer cells produce tumor necrosis factor-alpha (TNF alpha) upon exposure to LPS, and this cytokine has been implicated in liver injury from large doses of LPS, we tested the hypothesis that TNF alpha contributes to LPS enhancement of allyl alcohol hepatotoxicity. Rats were treated with LPS (10-100 microg/kg iv) 2 h before allyl alcohol (30 mg/kg ip). Co-treatment with LPS and allyl alcohol caused liver injury as assessed by an increase in activity of alanine aminotransferase in plasma. Treatment with LPS caused an increase in plasma TNF alpha concentration, which was prevented by administration of either pentoxifylline (PTX) (100 mg/kg iv) or anti-TNF alpha serum (1 ml/rat iv) one h prior to LPS. Only PTX protected rats from LPS-induced enhancement of allyl alcohol hepatotoxicity; anti-TNF alpha serum had no effect. Exposure of cultured hepatocytes to LPS (1-10 microg/ml) or to TNF alpha (15-150 ng/ml) for 2 h did not increase the cytotoxicity of allyl alcohol (0.01-200 microM). These data suggest that neither LPS nor TNF alpha alone was sufficient to increase the sensitivity of isolated hepatocytes to allyl alcohol. Furthermore, hepatocytes isolated from rats treated 2 h earlier with LPS (i.e., hepatocytes which were exposed in vivo to TNF alpha and other inflammatory mediators) were no more sensitive to allyl alcohol-induced cytotoxicity than hepatocytes from na?ve rats. These data suggest that circulating TNF alpha is not involved in the mechanism by which LPS enhances hepatotoxicity of allyl alcohol and that the protective effect of PTX may be due to another of its biological effects.     

Dose-independent pharmacokinetics of a new reversible proton pump inhibitor,KR-60436, after intravenous and oral administration to rats: gastrointestinal first-pass effect

Dose-independent pharmacokinetic parameters of KR-60436, a new proton pump inhibitor, were evaluated after intravenous (i.v.; 5, 10, and 20 mg/kg) and oral (20, 50, and 100 mg/kg) administration to rats. The hepatic, gastric, and intestinal first-pass effects were also measured after iv, intraportal (i.p.), intragastric (i.g.), and intraduodenal (id) administrations to rats of a dose of 20 mg/kg. The areas under the plasma concentration-time curve from time to zero to time infinity (AUCs) were independent of iv and oral dose ranges studied; the dose-normalized AUCs were 83.0-104 microg. min/mL (based on 5 mg/kg) and 78.4-96.8 microg. min/mL (based on 20 mg/kg) for iv and oral administration, respectively. After an oral administration at a dose of 20 mg/kg, approximately 3% of the oral dose was not absorbed, and the extent of absolute oral bioavaliability (F) was estimated to be 18.8%. The AUCs of KR-60436 after i.g. and i.d. administration at a dose of 20 mg/kg were significantly smaller (82.4 and 57.5% decrease, respectively) than that after an i.p. administration at a dose of 20 mg/kg, suggesting that gastrointestinal first-pass effect of KR-60436 was approximately 80% of oral dose in rats (the gastric first-pass effect was approximately 25%). After an i.p. administration at a dose of 20 mg/kg, the AUC was 77.6% of an iv administration, suggesting that hepatic first-pass effect was approximately 22% of KR-60436 absorbed into the portal vein. Note that the value of 22% was equivalent to approximately 4% of the oral dose. Because only 17% of oral dose was absorbed into the portal vein, the low F of KR-60436 in rats was mainly due to considerable gastrointestinal first-pass effect, which was approximately 80% (the gastric first-pass effect was approximately 25%) of oral dose.     

裂褶菌孢内多糖和孢外多糖对小鼠免疫功能的影响

裂褶菌孢内多糖(SPG₁)和孢外多糖(SPG₂)是分别从发酵培养的裂褶菌菌丝体和发酵液中提取的多糖。SPG₁和SPG₂均能显著促进Con A诱导的小鼠脾淋巴细胞增殖反应,SPG₁还显著地对抗氢可的松对淋巴细胞增殖反应的抑制作用。SPG₁和SPG₂均可恢复14月龄老年小鼠低下的脾淋巴细胞增殖反应。给小鼠ip SPG₁和SPG₂均能显著增强二硝基氯苯(DNCB)所致小鼠迟发型皮肤过敏反应(DCH)。小鼠ip SPG₁可显著增强羊红细胞(SRBC)诱导的小鼠脾脏空斑形成细胞(PFC)反应。SPG₁和SPG₂还可使老年小鼠的PFC反应恢复至成年小鼠水平。     

Dose-dependent and time-dependent pharmacokinetics in the dog after intravenous administration of dextrorphan.

The disposition of dextrorphan after single ascending iv doses and multiple iv dosing regimens was studied in Marshall beagle dogs. A dose-dependent decrease in plasma clearance was observed after the administration of single iv doses of 0.88 mg/kg, 2.64 mg/kg, and 8.8 mg/kg of dextrorphan (i.e. mean plasma clearance values +/- SD were 100 +/- 25 vs. 68 +/- 28 vs. 48 +/- 20 ml/min.kg, respectively; p less than 0.001). Upon multiple dosing, the plasma clearance of dextrorphan increased in a time-dependent fashion for the two highest doses, approaching values observed for the 0.88 mg/kg/day iv dosing regimen. Female dogs exhibited a greater increase in plasma clearance with time. For all dogs, however, dextrorphan plasma clearance approached or exceeded hepatic plasma flow rate, suggesting the possibility of extrahepatic metabolism or elimination. Modest dose- and time-dependent changes in the steady-state volume of distribution of dextrorphan also were observed. The AUC of the conjugated metabolites of dextrorphan decreased in a time-dependent manner for the 8.8 mg/kg/day dosing regimen. The nonlinear kinetics of dextrorphan after iv administration appeared to occur only after potentially toxic dosing regimens of dextrorphan hydrochloride. We postulate mechanisms to explain the dose- and time-dependent kinetics of dextrorphan observed in the beagle dog.     

Effect of amitraz on heart rate and aortic blood pressure in conscious dogs: influence of atropine, prazosin, tolazoline, and yohimbine

The effect of amitraz on heart rate (HR) and mean aortic blood pressure (MAP) were studied in five conscious male dogs. An iv injection of amitraz (1 mg/kg) caused a decrease in HR, which was accompanied by sinus arrhythmia for at least 60 min. Administration of amitraz also caused an increase in MAP for 20 min. Atropine sulfate (0.045 mg/kg, iv) increased HR and prevented amitraz-induced bradycardia. In addition, atropine potentiated amitraz-induced hypertension for 45 min. Yohimbine, an alpha 2-adrenoreceptor antagonist, given iv at 0.1 mg/kg, prevented hypertension, bradycardia, and sinus arrhythmia induced by amitraz. Tolazoline, a nonselective alpha-adrenoreceptor antagonist, given iv at 5 mg/kg, reduced the bradycardia and sinus arrhythmia caused by amitraz administration but did not change amitraz-induced hypertension. Tolazoline alone also increased both HR and MAP. Prazosin, an alpha 1-adrenoreceptor antagonist, given iv at 1 mg/kg, did not affect the cardiovascular actions of amitraz. The results suggest that (1) alpha 2-adrenoreceptors mediate amitraz-induced bradycardia and hypertension, and (2) yohimbine, but not atropine, can be used to control the untoward reactions of amitraz.