【作者】 周远洋；

【导师】 曾蔚越；

【作者基本信息】 四川大学 ， 妇产科学， 2007， 硕士

【摘要】 目的本课题拟选择临床应用多年的中药制剂——益母草注射液进行临床疗效研究，观察其对剖宫产妇女产时，产后促进子宫收缩，减少产时、产后出血的作用，进一步评价其对剖宫产妇女缩宫止血的有效性和安全性。同时以催产素为对照，观察益母草注射液对离体人子宫平滑肌收缩的幅度、张力、频率的影响，进一步阐明其作用机理。为产妇及产后出血患者提供有效、安全、药源丰富的中药制剂，以深入挖掘祖国医药尤其四川中医药，促进中医药现代化研究。方法选择2006年1月至2006年9月，四川大学华西第二医院孕龄＞28周，因医学指征或社会因素行剖宫产分娩者共278例，据末次月经、孕期B超结果等证实孕周无误，排除阴道分娩、孕龄不足28周和不愿意使用益母草注射液者。按入院先后依单双数编号，单数予以益母草注射液(试验组)共136例，双数予以缩宫素(对照组)共142例。观察指标包括剖宫产术中及术后2～72小时各时点出血量、子宫复旧、凝血功能改变，不良反应的发生。同时分为益母草注射液组和缩宫素组，分别将0.5ml及1ml缩宫素(10~U／ml)和益母草注射液(20mg／ml)加入20ml子宫肌蓄养液中，配成不同浓度药物，每组7例。观察用药前后子宫平滑肌收缩的频率、张力、强度、收缩幅度的改变。结果剖宫产术中出血量，试验组为279.44±151.77 ml，对照组为292.85±168.25 ml，二组之间无统计学差异(P＞0.05)。术后2h出血量，试验组52.49±55.20 ml，对照组54.30±72.39 ml(P＞0.05)；术中+术后2h总出血量试验组331.89±157.72 ml，对照组350.15±185.50 ml，二者无统计学差异(P＞0.05)。术后2～24h及至术后24h累计失血量二组无明显统计学差异(P＞0.05)。两组术后24～48h，48～72h及24h后总阴道流血量均不具有统计学差异(P＞0.05)。试验组术中宫壁追加注射宫缩剂1～2ml共7例(5.1％)，对照组术中追加宫缩剂1～2ml共14例(9.9％)(P＞0.05)。因宫缩乏力追加用药者，试验组1例(0.7％)与对照组5例(3.5％)无统计学差异(P＞0.05)；因出血过多者，试验组6例(4.4％)与对照组9例(6.3％)，无统计学差异(P＞0.05)。手术中到术后2h内总出血量大于400ml者试验组(27.2％)和对照组(30.3％)无明显差异(P＞0.05)；至术后24h内总出血量≥500ml者，试验组(20.6％)与对照组(26.8％)无统计学差异(P＞0.05)。术后24～72h总出血量不足50ml，50～100ml及≥100ml者，两组构成比无统计学差异(P＞0.05)。试验组宫壁注射后引起子宫开始收缩时间为2.61±1.05 min，对照组为2.40±0.83 min，二者比较无统计学差异(P＞0.05)试验组用药前后凝血功能无相关关系，用益母草注射液后PT、APTT延长，FIB减少，但前后改变无统计学意义(P＞0.05)；两组用药后未见发热、过敏、皮疹、继发出血、恶心、呕吐等症状及血压升高等不良反应，局部注射部位未见有红肿、硬结等异常反应，新生儿未见有与之确切相关的异常。对人离体子宫平滑肌研究显示，给药剂量为0.5ml时，可见益母草组(终浓度0.5mg／ml)和缩宫素组(终浓度0.25~U／ml)的子宫平滑肌收缩曲线均改变，波形强而有力，主要是收缩的幅度增大，张力及强度增加，而频率减慢。比较给药前后两组强度、张力、频率及子宫收缩幅度差值无统计学差异(P＞0.05)。益母草注射液终浓度为0.5mg／ml时，子宫平滑肌即可出现明显的节律性收缩，其强度、张力、幅度均较给药前增加，而频率减慢。幅度由给药前的441.3±205.0 mg增加到给药后的897.6±264.2 mg，增加了456.3±125.1 mg，二者比较有显著性差异(P＜0.05)；给药后频率为0.48±0.16次／min，较给药前的0.97±0.63次／min减少了0.50±0.60次／min，二者比较无显著性差异(P＞0.05)。和相应剂量缩宫素组给药前后宫缩幅度及频率变化比较，二者无显著性差异(P＞0.05)。予以1ml的缩宫素(10~U)和益母草注射液(20mg)，子宫平滑肌收缩曲线发生改变，表现为收缩的幅度增大，强度增加(图3，图4)。1ml缩宫素组(终浓度0.5~U／ml)子宫收缩幅度为2077.6±2220.8 mg，增加了1069.6±1125.1 mg，益母草组(终浓度1mg／ml)为1466.5±401.0 mg，增加了882.4±352.6 mg，二者无统计学差异(P＞0.05)。两组给药前后收缩幅度强度、张力及频率差值比较无统计学差异(P＞0.05)。增加益母草注射液剂量，可以观察到子宫收缩曲线的张力、强度、频率及幅度均较前有所增加，具体表现为子宫平滑肌收缩幅度由浓度为0.5mg／ml时的897.6±264.2 mg增加到浓度为1mg／ml时的1466.5±401.0mg，二者比较有统计学差异(P＜0.05)。给药后子宫收缩幅度，0.5ml益母草组增加了456.3±125.1mg，1ml益母草组增加了882.4±352.6 mg，二者比较有统计学差异(P＜0.05)。增加益母草浓度，表现出子宫收缩的强度变化幅度增加而频率减慢的趋势，但经统计学分析，无显著差异(P＞0.05)。结论益母草注射液可以促进子宫收缩，增加离体子宫收缩的张力、强度和幅度，用于剖宫产术中、术后有缩宫止血作用，与缩宫素合理搭配使用效果更好，有利于减少产后出血的发生。更多还原

【Abstract】 Objective:The purposes of the researching here were to make the research of theeffects and safety of Leonurine injection on uterine contraction andhemostatic effects in intra- and post-cesarean section delivery, and observethe effects of Leonurine injection on the tension, intension, amplitude andrat of myometrium contraction in order to illuminate the mechanism. Andthe aims of the researching are to provide the effective, safe and affluenttraditional Chinese medical preparation for parturient and patients with PPHto improve the modern research of the traditional Chinese medicine.Methods:From January to September 2006, 278 cases who received cesareansection delivery were collected and analyzed. The gestational weeks werecarefully checked by last menstrual period, fetal movement and ultrasound.The cases, with the exception of the vaginal delivery, less than 28 weeksand unwilling to use Leonurus injection, were divided into two groups:Leonurus group which were treated with Leonurus injection, and the groupwith oxytocin. The clinical observation indexes included bleeding volumes after the operation for 2～72 hours, uterus recovery, function of bloodcoagulation and untoward reaction. Meanwhile, the human myometriumwhich obtained in CSD were dissected into two myometrial strips andsuspended in 20ml organ bath in uterine solution under isometric conditions.Undergoing spontaneous contractions, myometrium were exposed toleonurous injection and oxytocin in the dose range of 0.5ml to 1 ml. The rat,tension, intension and amplitude of myometrial contraction were measured.Result:The bleeding volumes intra- and post-operation in Leonurus group was279.44±151.77 ml. There were no significant differences from those inoxytocin group(292.85±168.25ml) (P＞0.05) The hemorrhagic volume about2 hours after the operation in leonurus group was 52.49±55.20 ml and therewas no difference with oxytocine group (54.30±72.39 ml)(P＞0.05). Thebleeding volume of 2 to 72 hours after operation showed no differencebetween the two groups (P＞0.05).The cases of hemorrhagic volume more than 400ml were 27.2% and30.3% respectively from the operation to 2 hours later and were 20.6% and26.8% respectively to 24 hours later which the volume was more than 500ml. There was no significant difference in the incidence of postpartumhemorrhage between Leonurus group (20.6%) and oxytocin group (26.8%)(P＞0.05). No difference was demonstrated in the extra addition ofuterotonics during two groups (P＞0.05). The time of contraction after using uterine injection was as follows:2.61±1.05 minutes in the leonurus group and 2.40±0.83 minutes in theoxytocin group (P＞0.05).There was no change in the function of blood coagulation in theleonurus group. And no untoward reaction has been observed in the test.After exposure to a dose of 0.5ml leonurus, the uterine myometriumcontracted strongly. There was an apparent potential in the rate, tension,intension and amplitude of contractions. But two groups had no difference(P＞0.05). The contractive amplitude raised from 441.3±205.0 mg to897.6±264.2 mg after the exposure to 0.5mg/ml leonurus injection, andthere were obviously differences between two groups. The contractileamplitude was measured the increasing from 897.6±264.2 nag in 0.5mg/mlto 1466.53±401.0 mg in 1mg/ml leonurus injection, which had obviouslydisparity (P＜0.05). After increas the dose of injection, the tension, intensionof the uterine contraction seemed strongly while the rate showed smoothly,which have no differences between two density.Conclusion:The administration of leonurus injection intra-and post-operation mayimprove uterine contractility and have the effect on hemostasis intra- andpost-operation. And Leonurus injection can improve the uterine contractilityboth in vivo and ex vitro.更多还原