胶艾汤活性成分治疗子宫疾病的网络药理学研究

目的 采用网络药理学研究方法探究胶艾汤的药理作用机制。方法 依托中药系统药理学分析平台（TCMSP），检索胶艾汤7味中药的活性成分和基因靶点。采用Cytoscape构建化合物-靶点网络、化合物靶点-疾病靶点和靶点-通路网络，根据在线STRING数据库构建蛋白质相互作用网络，研究胶艾汤药理机制。结果 通过筛选获得64个化合物，化合物-疾病相应关键靶点32个。蛋白质相互作用网络包含20个靶点，关键靶点涉及Ptgs2、F2、Tnf、Il6、F3等。基因本体条目61个，其中生物过程相关的条目34个，细胞组成相关条目20个，分子功能相关的条目7个。KEGG通路富集分析通路4条。结论 本研究初步验证了胶艾汤的基本药理作用及其机制，为进一步探究其药理作用奠定了基础。     

化学修饰对组织型纤溶酶原激活剂的纤溶活性和体内半衰期的影响

用肝素、右旋糖酐和聚乙二醇对重组组织型纤溶酶原激活剂(rt-PA)进行化学修饰。不同的化学修饰物对rt-PA体外纤维蛋白溶解活性的影响不同。肝素修饰小PA的纤维蛋白溶解活性提高63％;右旋糖酐和聚乙二醇修饰rt-PA的纤维蛋白溶解活性则分别降低了36％和63％。rt-PA经化学修饰后半衰期均有所延长,其中聚乙二醇修饰的小PA的半衰期由修饰前的3．4min延长至6．3mim。     

胶艾汤与四物汤对子宫出血模型大鼠保血功效的比较研究

<正>胶艾汤首载于东汉张仲景《金匮要略》,四物汤首载于唐蔺道人《仙授理伤续断秘方》,由胶艾汤减阿胶、艾叶和甘草三味,干地黄易为熟地,芍药定为白芍而成。胶艾汤衍化为四物汤,主治病症由漏下、半产出血及妊娠下血、妊娠腹痛衍化为血虚血瘀、月经不调。前期试验研究表明胶艾汤衍化为四物汤后活血功效增强[1],本实验采用子宫出血动物模型评价胶艾汤衍化为四物汤前后的保血效应,以期为阐明两方衍化配伍机制[2]和临床合理用药提供依据。     

凝血酶原时间检测试剂不同溶解条件对检验结果的影响

目的本次实践研究,重点探讨分析凝血酶原时间检测试剂的不同溶解条件对检验结果的影响。方法主要采取回顾分析的方法 ,选取了2015年2月至2016年2月我院收治的需要进行凝血酶原时间检测的相关疾病患者80例,其中包括正常组和异常组,每组各40例患者。分别观察记录比较两组凝血酶原时间检测患者试剂在不同放置方法、溶解条件下,对其检验结果产生的影响。结果两组不同的凝血酶原时间检测试剂,在托盘上放置不同时间检测结果 ,包括16 h、18 h、20 h时间上,原试剂与新试剂检测结果进行比较,差异显著有统计学意义(P<0.05);在冰箱冷藏室中不同时间检测结果 ,包括56 h、64 h、72 h时间上,原试剂与新试剂检测结果进行比较,差异显著有统计学意义(P<0.05)。结论影响凝血酶原项目检测结果的因素是多方面的,为了能够得到更加精准的检验结果 ,以往每天检测一次是不够的,冰箱冷藏是保证其活性成分的最佳手段,在检测中需要将质控品随每批标本放在一起来检测,这样才可以获取更加准确的检验结果 ,帮助临床医师为患者提供有针对性的治疗方案。     

体外环境下纤溶酶及不同载药量对纤维蛋白胶缓释作用影响

目的：考察纤溶酶及不同载药量对顺铂-纤维蛋白胶复合物在体外缓释作用的影响。方法：采用衍生-紫外分光光度法对顺铂-纤维蛋白胶复合物体外释放样本进行测定。观察纤溶酶对不同栽药量纤维蛋白胶（6-bfin出ue,简称FG）的释放过程是否存在影响。结果：溶介为纤溶酶时早期（24h）药物释放相对较快,1h和24h时间点溶液中药物浓度存在差异（P〈0．05）。结论：体外环境下纤溶酶对顺铂-纤维蛋白胶复合物（CDDP／FG）缓释过程早期存在影响。不同栽药量对其缓释作用无影响。     

自制黄艾汤用于子宫不同位置药物流产后的临床效果观察

目的：观察自制黄艾汤用于子宫不同位置药物流产后的临床效果。方法282例药物流产患者随机分为观察组和对照组,各141例。对照组服用米非司酮和米索前列醇进行治疗,观察组在此基础上服用自制黄艾汤治疗。观察两组阴道流血量、阴道流血时间、流产情况。结果①观察组出血量少、量中发生率明显低于对照组(P<0.05);阴道流血时间短于对照组(P<0.05);完全流产率明显高于对照组(P<0.05)。②子宫前倾位和子宫后倾位分别与子宫前屈位和子宫后屈位比较完全流产率明显增高,差异有统计学意义(P<0.05)。结论自制黄艾汤用于流产后能有效减少阴道流血量,缩短阴道流血时间,提高完全流产率,值得临床广泛应用,且子宫位置对流产效果有一定影响,子宫前倾位和子宫后倾位流产效果明显高于子宫前屈和子宫后屈位。     

复方茯苓汤不同组方配伍对变应性接触性皮炎模型小鼠血清中IFN-γ、IL-4、IL-10水平的影响

目的：揭示复方茯苓汤不同组方配伍对变应性接触性皮炎（ACD）模型小鼠的影响。方法：采用2,4-二硝基氟苯制备ACD小鼠模型,观察不同组方的中药对ACD小鼠血清中IFN-γ、IL-4、IL-10水平的影响。结果：全方组、5味药组、氢化可的松组和模型对照组比较,对ACD小鼠有显著抑制作用。结论：初步确定复方茯苓汤的主要药效成分来源于茯苓、当归、栀子、赤芍和甘草5味中药。     

复方桑钩颗粒对高血脂大鼠纤维蛋白原、抗凝血酶-Ⅲ及纤溶活性的影响

目的:探讨复方桑钩颗粒对高血脂大鼠纤维蛋白原(Fib)及抗凝血酶Ⅲ(AT-Ⅲ)、组织型纤溶原激活物(t-PA)、组织型纤溶原激活物抑制剂-1(PAI-1)水平的影响。方法:采用高脂饲料喂养建立高血脂症病理模型。SD雄性大鼠60只随机分为正常对照组、模型空白组、复方桑钩颗粒高剂量组、低剂量组和氟伐他汀钠组,每组12只。给药4周后采血测定各组大鼠血脂水平、Fib含量、AT-Ⅲ、t-PA、PAI-1及t-PA/PAI-1比值。结果:与正常对照组比较,模型空白组大鼠血脂总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)明显升高(P<0.01),高密度脂蛋白胆固醇(HDL-C)明显降低(P<0.01)。模型空白组Fib含量、PAI-1值较正常对照组明显增加;AT-Ⅲ活度、t-PA值、t-PA/PAI-1比值则较正常对照组明显降低(P<0.01)。高剂量组的TC、LDL-C、PAI-1、Fib与模型空白组比较,水平明显降低(P<0.01或0.05),HDL-C、t-PA、t-PA/PAI-1、AT-Ⅲ则明显升高(P<0.01或0.05);低剂量组大鼠的TC、LDL-C、PAI-1水平明显降低,t-PA/PAI-1显著升高(P<0.01),其他无明显影响。氟伐他汀钠组除AT-Ⅲ水平无显著影响(P>0.05)外,其余各指标的变化与高剂量组相当。结论:复方桑钩颗粒在降低高血脂模型大鼠血脂的同时,能改善高血脂大鼠的高凝状态、提高抗凝和纤溶能力,尤其是高剂量组,效果与氟伐他汀钠相当,在抗凝方面甚至优于氟伐他汀钠。     

胺碘酮对兔缺血再灌注纤溶活性、内皮血管活性物质的影响

目的探讨兔缺血再灌注纤溶活性、内皮血管活性物质的变化及胺碘酮的影响。方法新西兰大白兔60只,随机分为5组,每组12只,Ⅰ组:假手术组,Ⅱ组:急性心肌梗死(acute myocardial infarction,AMI)组,Ⅲ组:缺血再灌注(ischemic reperfusion,IR)组,Ⅳ组:IR+利多卡因组,Ⅴ组:IR+胺碘酮组;各组(除Ⅰ组外)分别结扎冠状动脉左室支中点,缺血60min,再灌注240min(Ⅰ,Ⅱ组不进行再灌注),分别取结扎前、再灌注前、再灌注240min血测定内皮素(endochelin,ET)、一氧化氮(nitricoxideNO)浓度和组织型纤溶酶原激活剂(tissue-type plasminogen activator,t-PA)、纤溶酶原激活剂抑制物(plasminogen activator inhibitor PAI)活性。结果冠状动脉结扎后,血浆ET,NO浓度和PAI活性显著高于结扎前(P<0.01),t-PA活性显著低于结扎前(P<0.01),再灌注后,血浆ET,NO浓度和PAI活性进一步升高,t-PA活性进一步下降,与再灌注前对比均有显著性差异(P<0.01)。再灌注后,与IR组对比,胺碘酮能显著降低血PAI活性和ET浓度(P<0.01);利多卡因组无显著变化。结论胺碘酮可抑制缺血再灌注过程中PAI活性、抑制内皮细胞释放ET的有益作用。     

益母草倍半萜化合物对大鼠凝血功能和子宫活动的影响

目的:初步探讨益母草倍半萜化合物的调经活血活性。方法:从益母草药材中提取分离得到2个倍半萜化合物Chamigrenal(简写为YMC-4)和(2S,5S)-2-hydroxy-2,6,10,10-tetramethyl-1-oxaspiro[4.5]dec-6-en-8-one(简写为YMC-6),经核磁技术鉴定结构。制备大鼠血清,采用全自动血凝仪测定两个化合物对体外凝血功能(PT、a PTT、TT)的影响;采用血小板聚集仪测定两化合物对二磷酸腺苷(ADP)诱导的血小板最大聚集率的影响;采用十六道生物机能系统观察其对大鼠离体子宫收缩频率、幅度(最大值、最小值、平均值)和活动力的影响。结果:在终浓度为1×10-5 mo L.L-1时,与溶剂对照组比较,YMC-6可明显降低ADP诱导的血小板最大聚集率和延长PT值,具有统计学意义(P0.05),YMC-4作用不明显;YMC-6可明显提高缩宫素致痉挛大鼠子宫收缩平均值、频率和活动力,YMC-4则明显抑制痉挛大鼠子宫收缩最大值,与溶剂对照组比较均有显著性差异(P0.05或P0.01);二者对正常大鼠离体子宫活动呈抑制趋势。结论:益母草倍半萜化合物是益母草调经活血的物质基础之一。     

磷酯酶C对实验性血栓形成和纤溶功能的影响

磷酯酶Ｃ(ｐｈｏｓｐｈｏｌｉｐａｓｅＣ ,ＰＬＣ)是一类作用于磷脂Ｃ3磷酯酰键的脂类水解酶 ,具有多种生物功能 ,研究表明 ,ＰＬＣ具有抗凝血及延缓血小板聚集的功能[1,2 ] 。通过体内、外两种给药途径研究了ＰＬＣ对实验性静脉血栓形成及纤溶功能的影响。希望通过这些临床前药理研究 ,为将ＰＬＣ开发成为具有自主知识产权的创新药物提供有益的参考。1　材料和方法1 1　试剂　尿激酶 (南京大学药厂 )、凝血酶 (华中科技大学同济医学院血液研究所 )、人纤维蛋白原 (中国药品生物制品检定所 )、普鲁卡因 (武汉滨湖制药厂 )、苯巴比妥钠 (上海…     

莲心碱对血小板聚集、凝血功能和血栓形成的影响

目的探讨莲心碱对大鼠体内血小板聚集和凝血功能的影响,同时评价其抗血栓作用。方法以二磷酸腺苷(ADP)诱导血小板聚集,采用比浊法观察莲心碱对大鼠体内血小板1、5min聚集率和最大聚集率的影响;通过毛细管法和减尾法分别研究莲心碱对小鼠凝血时间和尾出血时间的影响,同时评价莲心碱对大鼠凝血酶原时间(PT)、活化部分凝血激酶时间(APTT)及凝血酶时间(TT)的影响;采用Chandler法及动静脉旁路模型研究莲心碱对大鼠体外血栓和动静脉旁路血栓形成的影响。结果莲心碱5mg·L-1和10mg·L-1均能明显抑制ADP诱导的大鼠体内血小板1、5min聚集率和最大聚集率;明显延长大鼠PT、APTT和TT;明显延长小鼠凝血时间及尾出血时间;不同程度抑制大鼠体外血栓和动静脉旁路血栓形成,减轻血栓湿重和干重。结论莲心碱可明显对抗血栓形成,并具有对抗血小板聚集和凝血作用。     

不同抗凝剂、放置时间及处理方法对血糖浓度的影响

目的 探讨离体静脉血液标本不同抗凝剂、放置时间及处理方法对血糖浓度的影响.方法 选取健康体检者空腹静脉血样120份,按真空采血管所含抗凝剂和标本处理方法的不同分为6组,每组20份：A组（绿管）、B组（灰管）、C组（黄管）、D组（红管）,以上4组标本处理方法为离心后室温放置;E组（绿管）、F组（灰管）,以上2组标本处理方法为不离心室温放置.分别在0h、2h、4h、6h、8h这5个时段测定各组血糖浓度,分析各组标本在放置2h、4h、6h、8h后血糖浓度与本组0h浓度的差异,血糖检测采用己糖激酶法.结果 6组标本中,A组、E组标本在不同放置时间血糖浓度差异有统计学意义（P＜0.05）,血糖浓度随放置时间的延长逐渐下降,在8h内分别下降13.88％和40.69％,下降速度分别为1.73％/h和5.09％/h;B组、C组、F组不同放置时间的血糖浓度差异无统计学意义（P＞0.05）;D组在放置2h血糖浓度与0h浓度相比差异无统计学意义（P＞0.05）,放置4h、6h、8h血糖浓度与0h浓度相比差异有统计学意义（P＜0.05）,8h内血糖浓度下降7.24％,下降速度为0.91％/h.结论 标本抗凝剂、放置时间及处理方法均可影响血糖浓度,应根据检测需要选择合适的采血管采血并尽快离心处理和检测.     

克罗米酚对子宫内膜发育、血管生成和子宫血流的影响

目的 研究克罗米酚对子宫血流、子宫内膜发育及血管生成的影响。方法 选有正常月经的妇女61例,其中对照组30例,试验组31例。观察2组受试者排卵日(LH 0)天子宫内膜厚度及回声类型,在LH 0天及种植窗期(LH 7)天观察激素环境、内膜厚度、子宫动脉和放射状动脉搏动指数、子宫内膜微血管密度。结果 LH 0天,试验组子宫内膜厚度为8.61mm,大于9 mm者占41.95％;对照组9-84 mm,大于9 mm者占76.67％(P<0.01)。试验组A型内膜占54.84％,对照组占83.33％,2组比较有显著性差异(P<0.05)。LH 7天,试验组期外内膜发生率为80.66％;对照组41.38％,2组比较有显著性差异(P<0.0001)。试验组子宫内膜微血管密度(MVD)为19.40;对照组30.52(P<0.001)。子宫动脉和放射状动脉搏动指数(PI)中位数:试验组分别为2.75和2.15;对照组分别为2.21和1.71(P<0.05),试验组PI大于3者所占比例增加。结论 克罗米酚使子宫内膜厚度及回声类型发生改变,内膜发育延迟,抑制子宫内膜血管生成,减少子宫血液灌注,可能损害了子宫容受性。     

The effect of anastrozole on the single-dose pharmacokinetics and anticoagulant activity of warfarin in healthy volunteers

AIMS: The aims of this study were to determine the effects of the nonsteroidal, selective aromatase inhibitor, anastrozole, at steady-state concentrations, on the pharmacokinetics and pharmacodynamics of warfarin, and to assess whether or not anastrozole alone has any anticoagulant activity. METHODS: This was a randomized, double-blind, placebo-controlled, two-way crossover trial conducted at a single centre. The study comprised two treatment periods of 11 days, separated by a 3 week washout. Healthy male volunteers (n = 16, median age 28.5 years) were randomized to receive either anastrozole (7 mg loading dose on day 1, followed by 1 mg daily on days 2-11) in the first treatment period and placebo in the second treatment period, or vice versa. In addition to their randomized treatment, all volunteers received a single dose of 25 mg warfarin on day 3 of each treatment period. Blood samples for pharmacokinetic and pharmacodynamic assessment were taken at frequent intervals during each treatment period. The safety of volunteers was monitored throughout the study. RESULTS: Administration of anastrozole resulted in no clinically significant changes in the pharmacokinetics of either R- or S-warfarin compared with placebo for AUC (ng ml-1 h) (glsmean, R-warfarin; anastrozole 93619.9, placebo 91127.91, 95%CI 0.988-1.068; S-warfarin; anastrozole 57129.21, placebo 55676.34, 95%CI 0.979-1.076), CL/F (ml min-1) (glsmean, R-warfarin; anastrozole 2.23, placebo 2.29, 95%CI 0.937-1.012; S-warfarin; anastrozole 3.65, placebo 3.74, 95%CI 0.929-1.021) and t1/2 (h) (lsmean, R-warfarin; anastrozole 55.40, placebo 55.15, 95%CI-2.083-2.592; S-warfarin; anastrozole 39.38, placebo 40.98, 95%CI-6.189-2.996). In addition, anastrozole had no clinically significant effect on the pharmacodynamic effects of warfarin, as assessed 240 h after warfarin dosing by measurement of prothrombin time (s) (glsmean, anastrozole 11.56, placebo 11.31, 95%CI 0.987-1.059), thrombin time (s) (glsmean, anastrozole 19.06, placebo 18.75, 95%CI 0.980-1.054) activated partial thromboplastin time (s) (glsmean, anastrozole 29.94, placebo 29.74, 95%CI 0.968-1.047) and factor VII (%) (glsmean, anastrozole 97.81, placebo 107.26, 95%CI 0.821-1.012). Anastrozole alone had no effect on these indicators of the clotting process. CONCLUSIONS: Overall, there was no evidence to suggest that anastrozole has any clinically relevant effects on the pharmacokinetics of warfarin. Anastrozole had no effect on clotting mechanisms or on the pharmacodynamic activity of warfarin, as assessed by prothrombin time, thrombin time, activated partial thromboplastin time, and factor VII.     

Effects on fibrinolytic activity of corn oil and a fish oil preparation enriched with omega-3-polyunsaturated fatty acids in a long-term study

Summary

In addition to their beneficial effects in reducing platelet responsiveness, it has been a matter of controversy whether polyunsaturated fatty acids impair the fibrinolytic system or not. In a double-blind, parallel clinical trial, 40 subjects were randomized to treatment with 6?g/day of corn oil, or to 6?g/day of a fish oil preparation, enriched with omega-3-polyunsaturated fatty acids (2.0?g/day of omega-3-PUFA). Clinical and fibrinolytic variables were measured before and after 5 months of treatment. In the corn oil group, plasminogen activator inhibitor (PAI-1)decreased significantly but in the cod liver oil group, PAI-1 remained unchanged. Activities and mass concentrations of tissue plasminogen activator (t-PA) were unchanged in both groups. It is concluded that, in the doses given here, both these preparations have small or no effects on the fibrinolytic system.     

Effects of 17β-estradiol and progesterone on mitogen-activated protein kinase expression and activity in rat uterine smooth muscle

Activation of mitogen-activated protein kinases (MAPKs) is a critical event in mitogenic signal transduction. MAPKs are activated by tyrosine phosphorylation and translocate to different cellular compartments affecting protein function and gene expression. MAPK expression and activity was examined in uterine smooth muscle from rats pretreated with estradiol-17β alone or with estradiol-17β and progesterone. MAPK expression was detected by immunoblotting using erk 1/2 antibodies. MAPK activity was detected by measurement of the phosphorylation of a MAPK-specific peptide sequence of myelin basic protein. Steroid treatment caused a modest (20%) decline in erk 1 and 2 expression in membrane and cytosolic fractions. Both estrogen and progesterone increased MAPK tyrosine phosphorylation and membrane-associated MAPK activity. Steroid treatment increased cytosolic MAPK tyrosine phosphorylation, but not enzymatic activity. These data suggest that gonadal steroid hormones, which stimulate uterine hypertrophy, may exert their hypertrophic effects by increasing MAPK activity.     

倒卵叶五加大孔树脂不同体积分数乙醇洗脱组分对血小板聚集率及纤溶活性的影响

目的研究倒卵叶五加提取物D101大孔树脂不同体积分数乙醇洗脱组分对血小板聚集率及纤溶活性的影响。方法采用体外实验,比浊法测定倒卵叶五加提取物0%~80%不同体积分数乙醇洗脱组分在ADP聚集诱导剂作用下的血小板聚集率;采用纤维蛋白平板法测定倒卵叶五加提取物0%~80%不同体积分数乙醇洗脱组分纤溶活性。结果倒卵叶五加提取物体积分数10%~70%乙醇洗脱组分可明显抑制血小板聚集(P<0.05或P<0.01);体积分数20%~40%乙醇洗脱组分抗血小板聚集作用最强(P<0.01);体积分数20%~60%乙醇洗脱组分可明显提高纤溶活性(P<0.05或P<0.01);体积分数20%~50%乙醇洗脱组分纤溶活性最强(P<0.01)。结论倒卵叶五加具有明显的抗血小板聚集以及提高纤溶活性的作用,其作用与洗脱剂不同体积分数乙醇中的组分不同有关。     

Effect of felodipine,a new calcium channel antagonist,on platelet function and fibrinolytic activity at rest and after exercise

Summary Fourteen healthy male volunteers (age 21–29 years, mean 23.7 years) were given placebo for 14 days followed immediately by felodipine 5 mg b.d. for a further 14 days. After each period of treatment blood for analysis was taken at rest and after exercise on a cycle ergometer. Platelet aggregation, plasma beta-thromboglobulin (B-TG), platelet factor 4 (PF-4), adrenaline and noradrenaline, and serum thromboxane B₂ (TXB₂), 6-keto-prostaglandin (F₁ (6-keto-PGF₁), and euglobulin clot lysis time (ECLT), were measured on each occasion. The ECG, heart rate and blood pressure were monitored during the exercise tests.After felodipine therapy there was a significant decrease in the plasma level of PF-4 and B-TG at rest. This effect was maintained during exercise. There was no significant change in platelet aggregation, ECLT, TXB₂ or 6-keto-PGF₁ at rest or during exercise. Irrespective of therapy, the plasma levels of adrenaline and noradrenaline were increased and the ECLT was decreased when measured immediately after exercise.Thus, felodipine in modest therapeutic dosage decreases the plasma levels of B-TG and PF-4, indicating an inhibitory effect on platelet on release. The effect also occurred during exercise. Felodipine did not change fibrinolytic activity or the production of TXB₂ or 6-keto-PGF₁.