4′-甲基-7-(2-羟基-3-异丙胺基丙氧基)-黄酮盐酸盐对实验性血栓形成的影响

4′-甲基-7-(2-羟基-3-异丙胺基丙氧基)-黄酮盐酸盐(SIPI-549)对大鼠和家兔实验性血栓形成有剂量(或浓度)依赖性的抑制作用。ⅳ7.5～20.0 mg/kg,使大鼠颈动—静脉旁路血栓湿重减轻。家兔半体内试验(ⅳSIPI-549 10 mg/kg),可使Chandler管中的雪暴现象出现时间和血栓形成时间延长,血栓湿重和干重减轻。家兔体外实验与半体内试验的结果基本一致。     

蛇床子素抑制血栓形成及其作用机制研究

目的研究蛇床子素抑制血栓形成及其可能的作用机制。方法利用大鼠静脉血栓形成模型和动-静脉旁路血栓形成模型测定给予蛇床子素10mg／kg、20mg／kg、40mg／kg后血栓湿重和干重，同时在动-静脉旁路血栓形成模型中测定大鼠血清NO含量，血浆TXB2和6-keto—PGF1α的含量。结果蛇床了素20mg／kg、40mg／kg组可以明显抑制大鼠静脉血栓形成，减轻血栓湿重和于重；蛇床子素10mg／kg、20mg／kg、40mg／kg组可以明显抑制大鼠动-静脉旁路血栓形成，减轻血栓湿重和干重，同时增加血清中NO的含量，降低血浆中TXB2的含量和增加血浆中6-keto—PGF1α的含量。结论蛇床子素可明显抑制大鼠血栓形成．其作用机制可能与增加血清中NO的含量，降低血浆中TXB2的含量和TXB2/6-keto—PGF1α的比值有关。     

4′-甲基-7-(2-羟基-3-异丙胺基-丙氧基)-黄酮盐酸盐对冠脉血流和家兔实验性心肌梗塞的影响

SIPI-549 is a new cOmpound. In Langendorff's isolated rabbit heart, SIPI-549 significantly increased coronary blood flow (p<0.01), but did not change themyocardium contractibility and heart rate. A study of the uptake of ~(86)Rb by the mouse heart showed a significant increase of nutritional blood flow in the SIPI-549 treated group (p<0.05). On intact dogs, SIPI-549 also showed a significant increase of coronary blood flow (p<.05) and decrease of coronary resistance (p<0.01), but no change of cardiac output and blood presure was observed.In the model of myocardial infarction by high level double-ligation of the anterior descending branch of the left coronary in rabbits, iv SIPI-549 (4.1 mg/kg) significantly reduced the ΣST, NST and NO The size of infarct myocardium was significantly reduced (p<0.05) 24 h after ligation of the coronary artery Similar results were found in the propranolol (1 mg/kg) group. However, no obvious difference between the two groups was observed.     

红景天苷对大鼠实验性血栓形成的影响及其作用机制

目的研究红景天苷对大鼠实验性血栓形成的影响及其作用机制。方法①采用体外血栓法,观察红景天苷对大鼠体外血栓长度和干、湿重的影响;②建立血瘀模型,观察红景天苷对血瘀大鼠血液黏度、红细胞比容、血小板聚集率和凝血时间的影响。结果①红景天苷5.0mg/kg和10.0mg/kg缩短体外血栓长度(P<0.05),降低体外血栓湿重和干重(P<0.05)。②红景天苷5.0mg/kg和10.0mg/kg可明显降低红细胞比容、血液黏度(P<0.05,P<0.01),降低血小板聚集率,延长凝血时间(P<0.05,P<0.01)。结论红景天苷具有抗血栓形成作用,其机制与降低血液黏度改善血液流变性有关。     

4′甲基-7-(2-羟基-3-异丙胺基丙氧基)黄酮盐酸盐的抗实验性心律失常作用

4'-甲基-7-(2-羟基-3-异丙胺基丙氧基)黄酮盐酸盐(SIPI-549)对乌头碱诱发的大鼠心律失常有预防作用,对氯化钡诱发的家兔心律失常有治疗作用,对哇巴因诱发的豚鼠心律失常则无明显作用。抗心律失常作用比普萘洛尔强,但比胺碘酮弱。对狗急性心肌梗塞后24 h 的心律失常,本品的抗心律失常作用比利多卡因弱,但负性频率作用比其为强。     

4′-甲基-7-(2-羟基-3-异丙胺基-丙氧基)-黄酮盐酸盐对冠脉血流和家兔实验性心肌梗塞的影响

4′-甲基-7-(2-羟基-3-异丙胺基-丙氧基)-黄酮盐酸盐(代号SIPI-549),是在4′-甲基立可定的基础上,由上海医药工业研究院合成的新化合物。本室已经证明SIPI-549具有明显的抗心律失常作用,且治疗指数较高。本文主要报道其对冠脉血流和实验性心肌梗塞的作用。药品和试剂     

复方藻酸双脂钠抗血栓作用的实验研究

目的探讨复方藻酸双脂钠(CoPss)对大鼠实验性血栓形成的影响。方法采用对大鼠连续两周灌胃给药,分别对体内,体外血栓形成的2种模型观察其药物作用,包括血栓的湿重,干重及两种模型血栓形成的时间。结果实验组大鼠体外形成的血栓其湿重和干重均低于生理盐水对照组(P<0.01)并可使大鼠体内血栓形成时间显著延长(P<0.01)。结论实验证明CoPss对血栓形成有抑制作用,且抗血栓作用与剂量有明显依赖关系。     

新型磺酰胺类化合物SZ427的抗血小板聚集作用

目的研究新型磺酰胺类化合物4-乙氧基-N,N'-二(4-吡啶乙基)-1,3-苯二磺酰胺(SZ427)的抗血小板聚集作用。方法在体外药效学实验中,采用血小板聚集分析仪观察化合物SZ427对花生四烯酸(arachidonic acid,AA)、二磷酸腺苷(adenonisine disphosphate,ADP)和胶原诱导的家兔血小板聚集的影响。在体内药效学实验中,通过小鼠尾静脉出血时间、大鼠颈总动脉血栓和小鼠急性肺血栓三种模型分别观察化合物SZ427对出血时间、血栓质量和死亡时间的影响。结果在体外药效实验中,化合物SZ427能显著抑制AA、ADP和胶原诱导的家兔血小板的聚集作用;在体内药效学实验中,化合物SZ427能延长小鼠尾静脉出血时间,具有抗血小板聚集作用;能减少大鼠颈总动脉血栓质量,抑制血栓形成;能显著延长急性肺血栓小鼠的死亡时间,明显降低死亡率。结论化合物SZ427能抑制慢性血栓和急性血栓的形成,具有抗血小板聚集的作用。     

蒲黄煎液的抗大鼠实验性血栓作用

目的研究蒲黄对大鼠血栓形成的影响。方法分别采用大鼠动静脉吻合血栓形成模型和电刺激损伤颈总动脉血栓模型实验方法,将SD大鼠随机分为空白对照组、阿司匹林阳性对照组(0.3 g/kg)、蒲黄煎液高剂量组(8 g/kg)、中剂量组(4 g/kg)、低剂量组(2 g/kg),各组动物连续灌胃给药7 d,末次给药后1 h建立模型,测定各组动物血栓湿重及血栓栓塞率;测定血浆凝血酶原时间(PT)、活化部分凝血酶时间(APTT)及凝血酶时间(TT)。结果蒲黄能抑制动静脉吻合血栓的形成,使血栓湿重降低,血栓抑制率达15%~43%;同时蒲黄降低了大鼠电刺激动脉血栓栓塞率,使大鼠APTT、PT、TT明显延长,且具有剂量依赖关系。结论蒲黄能够对抗在体实验性血栓的形成,其抗血栓机制可能与APTT、PT、TT指标的改变有关。     

TY602-1的抗凝血作用研究

目的:探讨TY602-1的抗凝血作用及其作用机制。方法:采用离体FⅩa酶活性测定法、小鼠体内凝血酶原时间(PT)、活化部分凝血酶时间(APTT)和凝血酶时间(TT)的测定实验、大鼠动静脉旁路丝线上血栓形成实验、大鼠下腔静脉血栓模型实验,观察TY602-1的抗凝血药效。结果:TY602-1能抑制FⅩa活性;口服1.25,2.5,5和10 mg·kg-1剂量时明显延长小鼠PT和APTT,但对TT无明显影响;口服10 mg·kg-1剂量能明显抑制大鼠动静脉旁路血栓和下腔静脉血栓形成。结论:TY602-1是一种具有较强抗凝血作用的FⅩa抑制剂,可作为预防和治疗深度静脉血栓和肺动脉栓塞的药物使用。     

硫代脯氨酸对血栓形成和血小板功能的影响

采用Chandler法测定体外血栓形成,硫代脯氨酸体外浓度为1g/L或iv 25mg/kg可使兔或大鼠Chandler环中形成的血栓长度缩短、血栓湿重和干重减轻;采用旋转法测定血小板粘附性,硫代脯氨酸浓度为1g/L时使兔血小板粘附性降低;采用比浊法测定血小板聚集性,硫代脯氨酸体外浓度为1g/L PRP或iv50mg/kg均明显抑制ADP诱导的兔血小板聚集。     

SIPI—644对乌头碱诱发大鼠室性心律失常的作用

用乌头碱诱发的大鼠室性心律失常模型观察了SIPI-644十二指肠给药(id)的抗心律失常作用。本品id 50,100和200 mg/kg,均能显著对抗乌头碱诱发的各种室性心律失常,但三个剂量组之间没有明显差异p>0.05),抗心律失常作用的强度和剂量没有明显相关性。其id的药效比iv的药效弱,它和胺碘酮、静注的ED_(50)分别为12.3和27.8mg/kg,它们约TI分别为11.7和5.3。     

当归及其成分阿魏酸对大鼠血小板聚集和5-HT释放的影响

本文报告当归及其成分阿魏酸对大鼠血小板聚集性和5-HT释放反应的影响。结果表明,当归水剂在试管内当浓度为200～500mg/ml,阿魏酸0.4～0.6mg/ml时抑制ADP和胶原诱导的大鼠血小板聚集。静脉注射当归20g/kg 5分钟后对ADP和胶原诱导的大鼠血小板聚集有明显的抑制作用。阿魏酸钠0.2g/kg和0.1g/kg静脉注射时分别抑制ADP和胶原诱导的大鼠血小板聚集。用³H-5HT标记血小板,观察血小板聚集和释放反应的关系。当归水剂500mg/ml和阿魏酸钠1～2mg/ml对凝血酶诱导的血小板聚集有明显抑制作用,同时也抑制³H-5HT从血小板中释放。     

麝香酮在大鼠、家兔和狗体内的药代动力学

麝香酮在大鼠体内的药时过程符合二室开放模型,在家兔和狗体内的药时过程则符合三室开放模型。大鼠、家兔和狗之间的药代动力学过程存在着显著的种属差异,大鼠iv麝香酮12,18和24 mg/kg三种剂量间的药代动力学主要参数无显著性差异。iv给药大鼠的T_1/2B为118.1～131.2min。家兔和狗的T_1/2B分别为24.9和30.0 min,T_1/2γ分别为331.9和366.4 min。大鼠、家兔和狗三b种动物的V_ss分别为23.0,51.7和7.3 L/kg.V_c分别为2.33,2.13和0.38 L/kg。     

Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines,XXVI: Antiplatelet and Antithrombotic Effects of the Oligoamine RE 1492 in Combination with Standard and Future Antithrombotic Drugs

The combined effects of the oligoamine RE 1492 with the NO-donor RE 2047 or ASA, ticlopidine, pentoxifylline and BM 14515 were determined in vitro (Born-test and in vivo (rat thrombosis model). The effects in vitro were supra additive but over independent. In vivo all combinations showed over additive and over independent inhibition of thrombus formation. The best results were obtained with a combination of 10 mg/kg RE 1492C and 10 mg/kg RE 2047. It inhibited thrombus formation in arterioles (A) by 79 % and 36 % in venoles (V). The combined effect of RE 1492C and pentoxifylline 10 mg/kg each was 62% (A) or 32% (V), respectively.     

福定碱对大鼠学习和记忆的作用

用大鼠逃避反射及家免EEG等方法测试了从石杉科植物分离到的福定碱(fordine)对学习和记忆的作用,10～40μg/kg ip或20μg/kg po明显加快大鼠主动迥避反应形成速度,提高反应率;10～40μg/kg ip减少QNB破坏主动迴避反应的作用;20～40μg/kg iv对抗QNB和樟柳碱引起家兔EEG的变化。福定碱每天40μg/kg ip连续8天,大鼠脑与浆胆碱酯酶活力为正常的88.8±8.8%。福定碱有有效剂量小,安全系数大和口服有效的优点。以色林也加快大鼠主动迴避反应形成,但未能对抗QNB的破坏作用。     

Effects of scorpion venom bioactive polypolypeptides on platelet aggregation and thrombosis and plasma 6-keto-PG F1alpha and TXB2 in rabbits and rats.

Effects of scorpion venom active polypeptide (SVAP) from scorpion venom of Buthus Martensii Karsch of Chinese on platelet aggregation in ex vivo and vitro in rabbits, thrombosis in carotid artery of rats and plasma 6-keto-PG F1alpha and TXB2 in rats were studied by the turbidimetry, the duplicated thrombosis model by electrostimulation and RIA, respectively. The results showed that SVAP 0.125, 0.25, 0.5 mg/ml inhibited significantly the rabbit platelet aggregation triggered by 0.3 U/ml thrombin, 10 microM ADP in vitro (P<0.05 or 0.01) and SVAP at the dose of 0.32, 0.64 mg/kg iv prolonged distinctively the occlusion time of thrombosis that were induced by electrical stimulation. Increased% of 0.16, 0.32 and 0.64 mg/kg were 30.16, 71.74, 98.27%, respectively, which showed a good dose-effect relationship. SVAP 0.22 mg/ml (in vitro) or 0.2, 0.4 mg/kg (in ex vivo) could obviously increase the plasma concentration of 6-keto-PG F1alpha, but slightly effect rats plasma concentration of TXB2 in vitro and in ex vivo and significantly increase of value of PG I2/TXA2, which suggested that the mechanism of the antithrombotic action of SVAP is related to the resistance against platelet aggregation, increase of the concentration of PG I2 in plasma.     

盐酸青藤碱的抗心律失常作用

青藤碱(sinomenine,SIN),有多方面的药理作用,国内已有较系统的药理研究,但至今尚未见其抗心律失常作用的报道。本文在几种动物模型观察了SIN的抗实验性心律失常的效果。     

Toxicity of the Protein Kinase C Inhibitor Safingol Administered Alone and in Combination with Chemotherapeutic Agents

Safingol [(2S,3S)-2-amino-1,3-octadecanediol] potentiates thetoxicity of doxorubicin (DOX) and cisplatin (CIS) against tumorcells in vitro and in vivo. The present studies were conductedin rats and dogs to evaluate safingol toxicity when administerediv as a single agent and to evaluate safingol's ability to potentiatethe toxicity of established chemotherapeutic agents to normaltissues in vivo. In an escalating dose study, dogs were administeredsafingol iv at 5, 10, 20, 30, 40, and 75 mg/kg on Days 1 through6. Necropsies were performed on Day 7. Red urine was observedat 10 mg/kg and higher. Icterus was observed following 40 mg/kgwith additional signs of hypoactivity and anorexia occurringafter 75 mg/kg. Clinical and microscopic pathology revealedmarked hepatotoxicity, venous degeneration and necrosis at injectionsites, and evidence of intra-vascular hemolysis. Doses of 5,20, or 40 mg safingol/kg were utilized in single iv dose ratand dog studies. No evidence of adverse systemic toxicity wasseen up to 20 mg/kg in either species [for rats: C_max = 12,600(males) or 17,133 (females) ng/ml, AUC = 3853 (males) or 4365(females) ng x hr/ml; for dogs: C_max = 2533 ng/ml, AUC = 2851ng x hr/ml (no sex differences)]. Local effects of venous irritationor intravascular hemolysis were observed at all doses in ratsand at 20 and 40 mg/kg in dogs. A dose of 40 mg/kg [for rats:C_max = 31,233 (males) or 91,300 (females) ng/ml, AUC = 11,519(males) or 18,620 (females) ng x hr/ml; for dogs: C_max = 9033ng/ml, AUC = 11,094 ng x hr/ml (combined sex)] was associatedwith clinical pathologic and renal histomorphologic changesconsidered consequent to intravascular hemolysis in both species,lethality and testicular toxicity in rats, and clinical biochemicalchanges indicative of hepatobiliary injury in dogs. Studiesindicated that hemolysis occurred during infusion, was not causedby circulating levels of safingol, and was a function of doseconcentration and vein of delivery. Safingol at 10 or 20 mg/kgwas administered iv to rats 30–60 min prior to myelosuppressiveiv doses of DOX, CIS, or cyclophosphamide (CYP). Hematology,plus renal function and morphology for CIS-treated animals,was assessed 4 and 14 days later. Safingol did not potentiateDOX-, CIS-, or CYP-mediated leukopenia/thrombocytopenia. A minimalenhancement of CIS-mediated decrease in GFR and increase increatinine was observed at 20 mg safingol/kg. Dogs were administered20 mg safingol/kg iv followed 60 min later by 0.5 or 1.25 mgDOX/kg or 0.75 or 2.0 mg CIS/kg. A complete toxicologic assessment4 and 29 days postdose failed to show potentiation of DOX toxicityby safingol or vice versa. A renal lesion was inferred in dogsadministered 20 mg/kg safingol and 2 mg/kg CIS based on minimalto slight renal tubular regeneration observed 4 weeks post-treatment.There were no effects of safingol on the pharmacokinetic profilesof DOX or CIS or vice versa.