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。     

甘糖酯的溶栓作用以及对纤溶功能的影响

iv 甘糖酯50 mg/kg和25 mg/kg 能明显加速兔实验性肺动脉血栓栓塞的溶栓作用。体外溶栓实验表明,甘糖酯25 mg/ml 溶栓作用明显强于等抗凝效价的肝素。iv 甘糖酯25 mg/kg 和6.25 mg/kg 可使家兔血浆 ELT 缩短,血清 FDP 含量增加,血浆 Fg 含量减少。提示甘糖酯能提高纤溶功能并具有良好的溶栓作用。     

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...     

红霉素、苯巴比妥对氨茶碱药代动力学的影响

我们对比了家兔服用红霉素或苯巴比妥前、后氨茶硷药代动力学的变化。其中5只家兔在服用红霉素7天的前、后分别静脉注射氨茶硷25mg/kg;另外6只家兔在口服苯巴比妥14天的前、后分别静脉注射氨茶硷25mg/kg。在氨茶硷每次注射后的6小时内,分次取血清标本检测。结果表明,红霉素明显减少氨茶硷的清除率(P<0.001),并增加t(1/2)(P<0.05);苯巴比妥明显增加氨茶硷清除率(P<0.01),并减少t(1/2)(P<0.05)。     

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。     

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。     

水蛭注射液抗血栓与抗凝血作用

目的研究水蛭注射液的抗血栓和抗凝血作用。方法采用体外血栓法、纤维蛋白平板法及全血血块法,观察水蛭注射液的抗血栓作用;采用家兔血浆复钙时间法、凝血酶时间法及凝血酶原时间法,观察水蛭注射液的抗凝血作用。结果水蛭注射液高剂量(1.0 kg.L-1)、中剂量(0.5 kg.L-1)和低剂量(0.25 kg.L-1)均能明显溶解体外血栓(P<0.001)、纤维蛋白平板(P<0.001)和全血凝块(作用显著);能显著延长家兔血浆复钙时间、凝血酶时间和凝血酶原时间(P<0.001)。结论水蛭注射液具有较强的抗血栓和抗凝血作用。     

甘糖酯的抗血栓作用及其作用机理

本文研究了硫酸甘糖酯(PGMS)对家兔实验性血栓形成及急性实验性肺动脉血栓栓塞的影响,并与等抗凝效价肝素进行了比较。结果提示,PGMS具有较好的抗血栓作用。为探讨其作用机理,还观察了PGMS对家兔凝血系统和纤维蛋白溶解系统的影响。研究结果提示,PGMS可通过抑制凝血系统和激活纤维蛋白溶解系统而发挥其抗血栓作用。     

N-V蛋白酶体内外纤维蛋白溶解活性的实验研究

目的研究NV蛋白酶对纤溶系统的影响。方法采用纤维蛋白平板法,观察NV蛋白酶体外溶解纤维蛋白的活性。通过一次静脉给药后不同时间测定家兔纤维蛋白原(Fg)、D二聚体(DDimer)的含量及血浆优球蛋白溶解时间(ELT),观察NV蛋白酶对正常家兔纤维蛋白溶解活性的影响。通过测定家兔凝血酶原时间(PT)、活化部分凝血活酶时间(APTT),观察NV蛋白酶对凝血功能的作用。结果NV蛋白酶具有体外溶解纤维蛋白的活性,测定效价为30000kU·g-1。NV蛋白酶(6000U·kg-1体重,15000U·kg-1体重)可明显减少DDimer、Fg含量,缩短ELT,对PT、APTT无明显影响。结论NV蛋白酶具有纤维蛋白溶解活性,对凝血功能未见有影响。     

益气清肝汤联合恩替卡韦治疗慢性乙型肝炎肝纤维化的临床研究

目的观察益气清肝汤联合恩替卡韦治疗慢性乙型肝炎肝纤维化的临床疗效。方法慢性乙型肝炎肝纤维化76例随机分为对照组和观察组,观察组采用益气清肝汤联合恩替卡韦进行治疗,对照组采用恩替卡韦治疗。观察治疗后两组血清肝纤维化指标和主要临床症状的变化情况。结果两组患者肝纤维化指标均较治疗前明显下降（P〈0.05）;治疗结束时观察组纤维化指标变化值与对照组比较差异有统计学意义（P〈0.05）。两组患者经治疗后血清HBV-DNA水平均明显下降,但转阴率无明显差异（P〉0.05）;两组主要临床症状均有明显改善,其中观察组在纳差和皮肤巩膜黄染消退方面显著优于对照组（P〈0.05）。结论益气清肝汤联合恩替卡韦治疗慢性乙型肝炎肝纤维化临床疗效较单独使用恩替卡韦更好。     

甘附冲剂抗大鼠心动过缓作用

目的：研究甘附冲剂（ganfu granule）抗心动过缓作用及作用机制。方法：用普萘洛尔（Pro）和乙酰胆碱制备大鼠心率减慢模型；用硫代巴比妥法测定脂质过氧产物丙二醛（MOA）含量，用Green法测NO的含量。结果：30～270mg／kg甘附冲剂可显著抑制Pro引起的大鼠心率减慢作用（P〈0．05或P〈0．01），并缩短乙酰胆碱引起的大鼠心动过缓的持续时间（P〈0．05或P〈0．01）；30、90、270mg／kg甘附冲剂可显著增加大鼠心肌组织中NO含量（P〈0．05或P〈0．01）和降低大鼠心肌组织中MDA含量的增高（P〈0．05或P〈0．01）。结论：甘附冲剂有明显的抗心动过缓作用，其作用与适度增加心肌中NO含量和抑制脂质过氧化有关。     

Effects of Rong Shuan capsule,Xue Zhi Kang capsule,Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite in rats

In the present study, we aimed to examine the effects of Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite (CAM). The traditional Chinese medicines (TCMs) Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule are widely used to treat cardiovascular disease in China. They are often prescribed in combination with clopidogrel, a common anti-platelet Western drug. We investigated the influence of the four TCMs on CAM pharmacokinetics following administration at human dose in rats. Pharmacokinetic parameters were determined following oral (PO) administration of clopidogrel (7.5 mg/kg) with or without Rong Shuan capsule (75 mg/kg, PO), Xue Zhi Kang capsule (60 mg/kg, PO), Xin Yuan capsule (120 mg/kg, PO), or Songling Xue Mai Kang capsule (150 mg/kg, PO). Compared with the animals in the control group, Xue Zhi Kang capsule significantly decreased the area under the plasma concentration-time curve (AUC0-t) of the CAM derivative by 25.4%. However, the t1/2 and Vz/F of CAM derivative were significantly increased by 43.6% and 70.7%, respectively. It was also observed that the pharmacokinetic parameters were altered in groups pretreated with Rong shuan capsule, Xin yuan capsule or Songling Xue mai kang capsule compared with the control group, but not significant. This study indicated that Xue Zhi Kang capsule had an effect on the formation and metabolism of CAM. Therefore, in the beginning of co-administration of Xue Zhi Kang capsule and clopidogrel, the anti-platelet efficacy might be compromised because of the decreased formation of CAM. Otherwise, long-time co-administration might lead to side effects by the prolongation of the t1/2 and Vz/F increase of CAM.     

唐草片对洛匹那韦在大鼠体内药代动力学的影响

本研究利用大鼠模型探索抗艾滋病辅助治疗中成药唐草片对抗病毒药洛匹那韦药代动力学的影响。大鼠随机分为洛匹那韦组（36 mg/kg）和唐草片联用洛匹那韦组（LPV：36 mg/kg,Tang herb：864 mg/kg）,灌胃给药,高效液相色谱法测定给药前后0,0.5,1,2,4,8,10,12,14,16,22小时的血药浓度,计算药动学参数。结果显示：唐草片与洛匹那韦合并用药后,洛匹那韦的峰浓度Cmax和曲线下峰面积AUC显著提高（P〈0.05）、半衰期t1/2z和达峰时间Tmax延长（P〉0.05）。本研究提示唐草片可延迟洛匹那韦的吸收、推迟达峰时间、提高生物利用度,具体作用机制需要深入研究,临床用药需要考虑相互作用。     

降脂益肝冲剂对非酒精性脂肪性肝炎大鼠肝脏PPARα mRNA表达的影响

目的观察降脂益肝冲剂对非酒精性脂肪性肝炎(NASH)大鼠肝脏过氧化物酶体增殖物激活受体α(PPARα)mRNA表达的影响,探讨其治疗NASH的机制。方法24只雄性Wistar大鼠随机分为3组:健康组普通饲料喂养,模型组和治疗组高脂饮食喂养。治疗组在高脂饮食13周末给予降脂益肝冲剂,同时模型组和健康组给予等量的生活饮用水灌胃,18周末处死各组大鼠。测定肝组织甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA)含量及血清肿瘤坏死因子(TNF)-α水平,反转录聚合酶链反应(RT-PCR)法检测肝组织PPARα mRNA相对含量。结果模型组大鼠肝脏PPARα表达明显减少,肝脏TG、TC、FFA及血清TNF-α水平明显增加;治疗组肝脏PPARα表达明显增强,其余指标均明显下降。结论降脂益肝冲剂能显著促进PPARα的表达,可能是治疗NASH的分子机制之一。     

Immunomodulatory effects of yun zhi and danshen capsules in health subjects--a randomized, double-blind, placebo-controlled, crossover study

Immunostimulating polysaccharides extracted from the Chinese medicinal plant Yun Zhi (Coriolus versicolor) have been found to enhance various immunological functions, and Danshen (Salvia miltiorrhiza) to show beneficial effects on the circulatory system. In the present clinical study, we investigated if regular consumption of Yun Zhi and Danshen capsules could improve cellular immunity in healthy subjects. One hundred healthy subjects were recruited to take Yun Zhi (50 mg/kg body weight) plus Danshen (20 mg/kg body weight) or placebo capsules daily for four successive months and, after a 2-month wash-out period, crossover to take placebo or Yun Zhi plus Danshen capsules for four successive months. Flow cytometry was used to assess the lymphocyte subtypes and concentration of T helper (Th) cell cytokines in culture supernatant. Gene expression of cytokines and cytokine receptors of peripheral blood mononuclear cells (PBMC) was analyzed by cDNA expression array. Results showed that regular oral consumption of Yun Zhi-Danshen capsules could significantly elevate PBMC gene expression of interleukin (IL)-2 receptor, increase the percentage and absolute counts of T helper cell and ratio of CD4(+) (T helper)/CD8(+) (T suppressor and cytotoxic T) cell, and significantly enhance the ex vivo production of typical Th1 cytokine interferon-gamma from PBMC activated by phytohemagglutinin and lipopolysaccharide (all p<0.005). Such consumption had no adverse effects on liver and renal functions, and the biochemical bone profile. Therefore, regular consumption of Yun Zhi and Danshen could be beneficial for immunological functions by potential enhancement of cell-mediated immunity in healthy subjects without any adverse effects.     

茵柴降脂汤治疗非酒精性脂肪性肝病临床疗效观察

目的：茵柴降脂汤对非酒精性脂肪性肝病（ nonalcoholic fatty liver disease ,NAFLD）患者的临床疗效观察。方法全部92例符合诊断标准的患者被随机分为治疗组和对照组,治疗组采用茵柴降脂汤治疗,对照组采用口服多烯磷脂酰胆碱胶囊治疗;以1个月为1个疗程,3个疗程结束后进行疗效统计分析。结果治疗后,两组患者的丙氨酸转氨酶（ ALT）、三酰甘油（ TG）指标、肝／脾CT值都有显著改善,且各组前后结果对比差异均有统计学意义（ P＜0．05）。治疗后两组差异无统计学意义（P＞0．05）,但治疗组的体质量指数（BMI）值改善优于对照组,治疗前后比较,差异有统计学意义（P＜0．05）。结论茵柴降脂汤在降低NAFLD患者血清中ALT、TG指标,提高患者肝／脾CT值方面与常规药物多烯磷脂酰胆碱胶囊效果相当,在降低BMI值方面效果优于多烯磷脂酰胆碱胶囊。     

二至芍药汤治疗功能失调性子宫出血220例临床观察

目的观察自拟二至芍药汤治疗功能失调性子宫出血的临床疗效。方法将420例功血患者随机分为两组：治疗组220例采用自拟二至芍药汤治疗,对照组200例采用人工周期疗法治疗,观察两组治疗前后的症状、体征及BBT的变化。结果治疗组总有效率为95.9%,显著高于对照组的73.5%（P〈0.01）差异具有统计学意义。结论二至芍药汤治疗功血疗效确切,组方简单,值得临床推广应用。     

The determination of glycyrrhizic acid in Glycyrrhiza uralensis Fisch. ex DC. (Zhi Gan Cao) root and the dried aqueous extract by LC-DAD

A rapid, sensitive and specific reversed phase high-performance liquid chromatographic (LC) method with photodiode array detection (DAD) has been developed for the determination of glycyrrhizic acid in both the raw herb and a commercially prepared dried aqueous extract of Glycyrrhiza uralensis Fisch. ex DC. root (Zhi Gan Cao, liquorice). It was determined that extracting the raw herb in aqueous methanol (50:50 v/v) by sonication for 2 x 30 min was the most efficient sample preparation. Baseline resolution of the glycyrrhizic acid peak was achieved on a Varian Polaris RP C18-A (250 mm x 4.6 mm, 5 microm packing) column using an isocratic mobile phase consisting of 0. v aqueous phosphoric acid and acetonitrile in the ratio 60:40 v/v. Chromatograms were monitored between 200 and 400 nm for peak purity assessments, with quantitation performed at 254 nm. Glycyrrhizic acid calibration curves in the concentration range of 14-558 microg/ml were prepared on the day of analysis. Curve fitting was by the least-squares method, with correlation coefficients of >0.9998 obtained each time. The average recovery at three spike levels (50, 100, 200%) was of 95.91+/-1.05% and 98.36+/-3.45% (+/-S.D., n=7) for the spiked raw herb and dried aqueous extract respectively. The limit of detection and limit of quantitation was 0.52 and 1.72 mg/g respectively for the raw herb, and 0.75 and 2.51 mg/g respectively for the dried aqueous extract. Identity confirmation of the chromatographic peak was achieved by (-) electrospray ionisation tandem mass spectrometry. The concentration of glycyrrhizic acid in the root and dried aqueous extract was found to be 31.1+/-0.2 and 40.4+/-0.3mg/g (+/-S.D., n=7) respectively.