毛冬青甲素对3’,5’—环一磷酸腺苷磷酸二酯酶活性的影响

为探讨毛冬青甲素提高血小板 cAMP 的含量的机理,实验通过测量经磷酸二酯酶(PDE)水解作用后剩余的 cAMP 量来计算 PDE 的活性,井探讨不同浓度毛冬青甲素对 PDE 活性的影响。实验结果表明:0.1g/L 及0.5g/L 两种不同浓度的毛冬青甲素溶液其被水解的 cAMP 量分别为91.90±7.91pmol 和66.40±2.84pmol,与对照组(128.00±7.38pmol)比较,p<0.05或 p<0.01。提示毛冬青甲素能抑制PDE 的活性,说明毛冬青甲素能提高血小板 cAMP 水平,抑制血小板的凝集作用是通过抑制血小板的3′,5′-环一磷酸腺苷磷酸二酯酶的活性而实现的。     

毛冬青甲素和硝酸甘油对花生四烯酸代谢的影响

本文主要研究了毛冬青甲素在体外及体内对活化血小板功能途径的二磷酸腺苷(ADP)诱导的血小板聚集的抑制作用及与前列环素(PGI_2)样物质的作用。提示毛冬青甲素在体内能抑制活化血小板功能途径的花生四烯酸(AA),同时在体内及体外能抑制ADP活化血小板功能的途径。采用放射免疫法测定了兔血浆中血小析噁A_2(TXA_2)和PGI_2代谢物TXB_2及6—keto—PGF_(1α)的水平。结果提示毛冬青甲素可能主要是通过促进动脉内皮生成前列环素,而产生其抗血栓作用的。     

毛冬青甲素治疗慢性盆腔炎的临床观察

应用中药毛冬青的提取物毛冬青甲素对54例慢性盆腔炎患者进行临床观察,结果表明:毛冬青甲素对慢性盆腔炎患者的症状与体征有明显的改善作用;毛冬青甲素组(28例),与妇炎康组(26例)疗效比较P<0.05。提示毛冬青甲素的疗效优于妇炎康;慢性腔盆炎患者的血液粘度增高与正常组比较,差异有显著性,经毛冬青甲素治疗后,上述指标有不同程度的下降。提示慢性盆腔炎可能与患者血液流变性异常有关,毛冬青甲素可改善盆腔炎患者异常增高的血粘度。     

毛冬青甲素对兔血小板生成血小板恶A_2作用的研究

<正> 毛冬青(llex Pubeseens Hook et Arn)为民间广泛应用的活血通脉,消肿止痛,清热解毒药。毛冬青甲素系从毛冬青中提取的一种有效成分,经化学半合成而制成。经药理实验证明有抗大白鼠实验性血栓形成、缩小大鼠心肌梗塞范围、保护豚鼠心肌急性缺血等作用。临床观察刘冠心病、心肌梗塞、脑血栓有明显的疗效。为了进一步阐明毛冬青甲素的抗血栓性疾病的作用机制,本试验用兔研究了毛冬青甲素在体内及体外对血小板生成血小板(口恶) A_2(TXA_2的)影响。     

毛冬青甲素抗血栓形成的作用机制研究

临床观察毛冬青甲素对血栓性疾病有明显的疗效。药理实验证明毛冬青甲素能使大白鼠实验性血栓形成变小。目前认为 TXA_2和 PGI_2对血栓形成具有重要意义。为了探讨毛冬青甲素抗血栓的作用机制,本文主要研究了毛冬青甲素对大鼠动脉生成前列环素(PGI_2)样物质的影响。实验证明毛冬青甲素在体内和体外均有增强动脉生成前列环素样物质的作用,此可能是其抗血栓形成的作用机制之一。     

毛冬青甲素对豚鼠心肌细胞动作电位的影响及其机理初探

本文试图从细胞水平上探讨毛冬麦甲素对心肌的作用机理。实验取豚鼠右心室乳头肌作离体恒速灌流,用电驱动诱发其动作电位,以玻璃微电极引导,观察动作电位复极化时程和有效不应期等变化。实验结果表明:毛冬青甲素有延长APD50、APD_(90)和ERP的作用;硝苯吡啶能全部阻断毛冬青甲素延长APD和ERP的效应:酚妥拉明能使毛冬青甲素的效应减弱;心得安基本不影响毛冬青甲素延长APD和ERP的作用.提示毛冬青甲素主要通过激活钙通道,促进Ca~( )内流起作用;其作用可能与α受体有关,但与β受体基本无关.     

实验性原位性肾炎的药物防治研究

本文用抑制TxA_2合成酶的药物——苄基咪唑(BIm)和抑制血小板聚集的活血化瘀中药藏红花、毛冬青甲素和丹参对实验性原位性肾炎模型进行了干扰,结果显示BIm,藏红花和毛冬青甲素组动物的尿蛋白显著低于对照组,肾小球中的免疫复合物吸收加速,病理组织损害亦较对照组有显著的改善,尿毒症的死亡率较对照组减少。但丹参组和对照组比较则无显著性差别。结论;藏红花、毛冬青甲素和BIm对实验性原位性肾炎有治疗作用。提示血小板和TxA_2在原位性肾炎发病机理和病情发展中起着重要的致病作用。     

毛冬青甲素体外给药对花生四烯酸诱导的兔血小板聚集和丙二醛生成的影响

研究了毛冬青甲素体外给药对花生四烯酸诱导兔血小板聚集和聚集液中过氧化脂质含量变化的影响。结果表明,毛冬青甲素在较大样本中可抑制花生四烯酸诱导的血小板聚集和过氧化脂质的生成,两者间具有一定的相关性,表明毛冬青甲素抗血小板作用可能与抑制过氧化脂质有关。由于后者的生成量与花生四烯酸代谢活性产物TxA_2的生成有近似等摩尔增加的关系,故推测毛冬青甲素对TXA_2的合成有阻断作用,这种作用可能为毛冬青甲素抗血小板功能的作用机制。     

毛冬青甲素对心衰模型兔心功能的影响

本文旨在建立压力负荷过重心表模型,并且通过无创性心功能的动态检测及常规病理等指标的观察,探讨毛冬青甲素(IA)对心衰模型的强心效应。结果表明:毛冬青甲素能提高心脏每搏排血量(SV)和心脏指数(CI),延缓毛冬青甲素组(毛甲组)兔心功SV、CI的下降:即时效应显示,IA给药后SV和CD逐渐升高,给药2小时后SV和CI达到最高峰,并接近术前正常值水平;在病理变化方面,由于IA的应用,毛甲组病理变化较对照组减轻,毛甲组心衰症候群得到不同程度的改善。提示毛冬青甲素有较好的强心作用。     

毛冬青甲素体外给药对花生四烯酸诱导的兔血小板聚集和丙二醛生成的影响

研究了毛冬青甲素体外给药对花生四烯酸诱导兔血小板聚集和聚集液中过氧化脂质含量变化的影响。结果表明,毛冬青甲素在较大样本中可抑制花生四烯酸诱导的血小板聚集和过氧化脂质的生成,两者间具有一定的相关性,表明毛冬青甲素抗血小板作用可能与抑制过氧化脂质有关。由于后者的生成量与花生四烯酸代谢活性产物TxA₂的生成有近似等摩尔增加的关系,故推测毛冬青甲素对TXA₂的合成有阻断作用,这种作用可能为毛冬青甲素抗血小板功能的作用机制。     

黑木耳抗动脉粥样硬化的实验研究

本文观察黑木耳对实验性动脉粥样硬化(AS)家兔AS病变及有关生化指标的影响。实验结果,黑木耳有降低血浆胆固醇(TC)、过氧化脂质(LPO)、血栓素A_2(TXA_2)的含量,提高前列环素/血栓素A_2(PGI_2/TXA_2)比值,减轻AS病变的作用。表明黑木耳具有抗AS作用。其机理可能是通过降血TC,保护动脉内膜,抑制血小板聚集,并由此抑制TXA_2合成;血TC降低亦可减少脂质过氧化,从而使环氧化酶、TXA_2合成酶活性降低,TXA_2合成减少。黑木耳通过以上途径维系PGI_2/TXA_2平衡,保护血管完整性的内环境相对稳定,对抗动脉粥样硬化的发生。     

舒喘灵对环加氧酶PGI2合成酶和TXA2合成酶活性的影响

取猪肺微粒体用体外方法观察了舒喘灵对花生四烯酸（ＡＡ）实验代谢中环加氧酶、前列腺素（ＰＧＩ_２）合成酶及血栓素 Ａ（ＴＸＡ_２）合成酶的作用。结果表明,当以 ＡＡ为底物反应时各组均无明显反应,而当以前列腺素内过氧化物（ＰＧＨ_２）为底物反应时,舒喘灵３ × １０~（－６）ｍｏｌ／Ｌ组６－酮基－ＰＧＦ_（１ａ）的生成量明显增加（Ｐ＜０．０５）。提示舒喘灵对ＡＡ代谢中环加氧酶和ＴＸＡ_２合成酶影响不大,而对ＰＧＩ_２合成酶的活性有促进作用,故使ＰＧＩ_２生成量增加,６－ｋｅｔｏ－ＰＧＦ_（１ａ）／ＴＸＡ_２比值增大,因此有利于纠正ＰＧＩ_２－ＴＸＡ_２的平衡失调。     

钙拮抗剂对实验性肝缺血再灌注损伤防护作用机制探讨

本文报道鲈通道阻滞剂维拉帕米对大鼠肝缺血再灌注损伤模型的影响。结果提示：维拉帕米可显著减少血清转氨酶、乳酸脱氢酶的溢出：减轻肝缺血再灌注后的肝细胞病理性损伤；明显降低肝组织钙、ＬＰＯ、ＴＸＢ２的升高；维持缺血再灌注肝组织ＳＯＤ活性。维拉帕米通过抑制肝缺血再灌注进钙内流、氧自由基产生，维持Ｔ／Ｋ平衡，对肝缺血再灌注损伤起到保护作用。     

Prostacyclin and thromboxane in diabetes

Concentrations of the stable antiaggregatory prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and of the proaggregatory thromboxane A2 metabolite thromboxane B2 were measured by radioimmunoassay in plasma from 53 diabetics. In 33 of these patients the ability of platelets to produce thromboxane B2 during spontaneous clotting was also studied. Plasma 6-keto-PGF1 alpha concentrations were higher (p less than 0.05) in the diabetics (mean 107.7 +/- SE 7.6 ng/l) than in non-diabetic controls matched for age and sex (87.5 +/- 4.7 ng/l), and diabetics with microangiography (n = 28) and higher (p less than 0.01) concentrations (124.3 +/- 10.8 ng/l) than those without microangiography (n = 25; 89.2 +/- 9.3 ng/l). Plasma thromboxane B2 concentrations were also higher (p less than 0.01) in the diabetics (mean 218.5 +/- SE 25.3 ng/l) than in the controls (127.7 +/- 9.8 ng/l), but this increase was not related to microangiography. The ability of platelets to generate thromboxane B2 did not differ between the diabetics (181.4 +/- 16.4 microgram/l) and controls (195.8 +/- 11.8 microgram/l). Platelets of diabetics with microangiopathy or taking oral hypoglycaemic agents (n = 19), however, produced decreased amounts of thromboxane B2 during clotting. Plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 were not related to concentrations of glucose, haemoglobin A1, high-density lipoprotein cholesterol, cholesterol, triglycerides, magnesium, or creatinine. These results suggest that in diabetics with microangiopathy a balance between prostacyclin and thromboxane A2 is shifted to dominance by prostacyclin.     

Biosynthesis of thromboxane in patients with systemic sclerosis and Raynaud's phenomenon

Thromboxane A2, the predominant cyclo-oxygenase product of arachidonic acid in platelets, is a potent vasoconstrictor and platelet agonist. Analysis of urinary metabolites by gas chromatography and mass spectrometry is a specific non-invasive method of measuring the biosynthesis of thromboxane that avoids the problem of platelet activation ex vivo. Excretion of the major urinary thromboxane metabolite, 2,3-dinor-thromboxane B2, was significantly increased (p less than 0.001) in 10 patients (nine women) with systemic sclerosis complicated by Raynaud's phenomenon compared with healthy controls (486 (SD 88) v 162 (38) ng/g creatinine) and increased further in the patients (to 1007 (212) ng/g creatinine) during application of a cold stimulus sufficient to induce digital vasoconstriction. Consistent with an increase in platelet-vascular interactions in vivo, excretion of a prostacyclin metabolite was also significantly increased (p less than 0.005) in the patients with systemic sclerosis (248 (39) v 112 (10) ng/g creatinine) and tended to increase further on cooling. Biosynthesis of thromboxane is increased in patients with systemic sclerosis and may exacerbate digital vasospasm that such patients develop when cold. This observation and the concomitant increase in the formation of prostacyclin provide a rationale for evaluating compounds that prevent the synthesis of thromboxane A2 or inhibit its action while preserving the potential homoeostatic role of prostacyclin.     

丁苯酞治疗急性脑梗死及其对血栓素A_2、前列环素及抗凝血酶Ⅲ的影响

目的观察丁苯酞治疗急性脑梗死的疗效及其对血栓素A_2(TXA_2)、前列环素(PGI_2)、抗凝血酶Ⅲ(AT-Ⅲ)的影响。方法将100例急性脑梗死患者随机分为对照组和丁苯酞组。对照组患者给予常规治疗;丁苯酞组在对照组治疗的基础上给予丁苯酞治疗。2组疗程均为21d。2组患者于治疗前后检测神经功能缺损评分(NIHSS)、日常生活能力评分(Barthel指数)、脑梗死灶体积、TXB_2、6-Keto-PGF1a及AT-Ⅲ。结果治疗21d后,丁苯酞组的总有效率90.0%高于对照组74.0%(P<0.05);丁笨酞组NIHSS评分、Barthel指数、梗死灶体积、TXB_2、6-Keto-PGF1α及AT-Ⅲ均显著改善(P<0.05,P<0.01),对照组除梗死灶体积、AT-Ⅲ外,余指标亦显著改善(P<0.05,P<0.01),丁苯酞组均优于对照组(P<0.01或P<0.05);且其不良反应轻微。结论丁苯酞联用传统药物治疗急性脑梗死安全有效,能显著改善神经功能和日常生活能力,缩小梗死灶体积,降低TXA_2,提高PGI_2及AT-Ⅲ水平。     

Effects of Codonopsis pilosulae on the synthesis of thromboxane A2 and prostacyclin

24 angina pectoris patients were treated with Codonopsis pilosulae (CP) oral solution 20 ml (containing crude CP 20 g) thrice daily for 7 days, other 10 cases were treated by aspirin 0.5 g per day for a week as the control group. After treatment, in the CP group, the plasma level of TXB2 was obviously reduced from 156.76 +/- 11.87 pg/ml to 125.01 +/- 8.85 pg/ml (means +/- S means), the inhibitory rates was 15. 67% (P less than 0.05), and of 6-keto-PGF1 alpha (6-K) was not markedly changed (P greater than 0.05). In the aspirin group, TXB2 was also reduced significantly (P less than 0.05); 6-K was reduced more than that of CP group, the inhibitory rate was 24.33 +/- 9.40% (P less than 0.05). To reveal the mechanism of CP action on the synthesis of TXA2 and PGI2, the porcine lung microsome was used as the donor of cyclooxygenase, thromboxane synthase and prostacyclin synthase, the effects of CP on the formation of TXB2 and 6-K from arachidonic acid (AA) or endoperoxides were measured by RIA respectively. The results showed that both the levels of the formation of TXB2 from AA or endoperoxides were markedly reduced by CP in a dose-dependent (at doses of 3-300 mg/ml). The synthesis of TXB2 was distinctly inhibited alone with a dose of 100 mg/ml CP, which suggested that CP might be an inhibitor of TXB2 synthase at that dose; while at a dose of 300 mg/ml CP, the synthesis of TXB2 and 6-K were inhibited simultaneously (P less than 0.001). It showed that a larger dosage of CP, which could inhibited the synthesis of both TXA2 and PGI2, its mechanism of action needs further study.     

参附注射液对肝缺血再灌注大鼠血浆前列环素和血栓素A2及肝组织ATP酶的影响

目的:探讨参附注射液对大鼠肝缺血再灌注损伤的保护作用及其机制。方法:24只Wistar大鼠随机分为模型组和参附注射液(Shenfu Injection,SF)治疗组。SF治疗组大鼠腹腔注射参附注射液10ml/kg。模型组大鼠给予相同剂量的生理盐水。两组均采用Pringle's法阻断肝门缺血15min再灌注1h和3h,测定血浆血栓素B2(thromboxane B2,TXB2)和6-酮-前列腺素F1α(6-keto-prosta-glandin F1α,6-keto-PGF1α)以及肝组织匀浆Na -K -ATP酶、Ca2 -Mg2 -ATP酶的变化,并观察肝组织形态学改变。结果:再灌注3h SF治疗组血浆TXB2低于模型组,6-keto-PGF1α高于模型组,两者比值TXB2/6-keto-PGF1α低于模型组;再灌注1h、3h SF治疗组Na -K -ATP酶和Ca2 -Mg2 -ATP酶活性高于模型组。SF治疗组肝实质细胞和线粒体损伤明显减轻。结论:参附注射液对肝缺血再灌注损伤有保护作用,其机制与降低TXA2/PGI2比值,提高Na -K -ATP酶和Ca2 -Mg2 -ATP酶活性有关。     

毛冬青甲素对家兔颈总动脉球囊成形术后PGI_2和TXA_2的作用

目的探讨毛冬青甲素(IA)抑制动脉成形术(BA)后再狭窄(RS)的作用。方法建立兔动脉粥样硬化模型,分为空白对照组(1组)、试验对照组(2组)、治疗组(3组)。1组仅结扎右颈外动脉。2组、3组予右颈总动脉球囊损伤,后者术当天起至术后4周口服IA。测定不同时期的血浆前列环素(PGI2)、血栓素A2(TXA2)水平,试验结束时行病理形态学检测。结果动脉BA术后血浆PGI2水平在2组较1组降低,3组的较2组的增高;血浆TXA2水平在2组较1组增高,3组的较2组的降低。2组的管腔面积和内弹力板围绕面积明显小于3组,3组的内膜面积明显小于2组。以上均有统计学差异。结论IA促进PGI2分泌,抑制TXA2释放,保持PGI2/TXA2的相对平衡,抑制BA后的RS。