【作者】 李滨；

【导师】 赵宏；

【作者基本信息】 河北医科大学 ， 外科学， 2004， 硕士

【摘要】 目的: 对心脏瓣膜置换术后预防栓塞的研究一直是人们重视的课题。血栓形成是由于正常的凝血机制被扰乱而促使某些血细胞和蛋白质被激活相互作用而最终导致血小板-纤维蛋白血栓，它不仅是多细胞类型参与，也是多代谢途径参与的过程。临床上采用维生素K拮抗剂香豆类药物以华法林为代表及抗血小板药物如阿司匹林，潘生丁等口服均有不同程度的不良反应如华法林容易导致出血，妊娠期间服用华法林对胎儿有无致畸作用一直存在争议。而阿司匹林可引起的的消化道的一系列副反应如出血、消化性溃疡等。而且华法林对参与白血栓形成的主要成分血小板并无抑制作用，因此有时配伍用阿司匹林，但阿司匹林对某些诱导剂如ADP诱导的血小板聚集的抑制作用较弱。近年来，随着对丹参、川芎等传统中药用途的开发研究不断深入，关于其在心血管系统的药理作用的实验依据也不断增多，其作用不仅表现在对心脏收缩力，频率以及血压的调节作用，还表现在通过抑制血小板聚集和抗脂质氧化物对血管内膜的损伤等作用从而抑制血栓形成和预防动脉粥样硬化的发生。这使我们认识到传统中药在防治血栓性疾病中的巨大潜力。祖国医学认为血栓属于血瘀范畴中医的“血瘀”与血小板高聚集状态、血液循环障碍及血栓形成有关而活血化瘀则与抑制血小板功能、改善血液循环障碍，防止血栓形<WP=4>成或使生成的血栓溶解有着密切的关系。同时气血之间存在着密切的关系，在生理上相互依存，气为血之帅，血为气之母，气滞则血瘀。在活血药中加入补益心气药，使气行则血行。丹芎抑凝饮由我省中医院研制通过选择丹参、川芎、水蛭、红花、桃仁等多味活血化瘀中药与补益心气党参、黄芪、白术、甘草、当归、白芍等中药配伍组成。在临床治疗血栓性疾病中取得了良好的效果。本次拟通过动物实验的方法研究其对家兔内源性、外源性凝血途径、血液流变学的各种参数的研究并将其结果与华法林进行同步比较。以验证此种抗凝中药的抗凝作用以期为其在临床的进一步应用和开发提供实验依据。 方法：对家兔凝血酶原时间(PT)及活化部分凝血活酶时间(APTT)的测定：家兔随24只机分成四组，设空白对照组、阳性对照华法林组，丹芎抑凝饮根据服用中药剂量不同设高低两个剂量组，每组6只。各组按公斤体重灌胃给药。每日一次，连续7天，于第3、5、7天给药后一小时的分别于兔耳部中心动脉取血由ACL-200(美国贝克曼)型智能血液凝集仪检测测量PT、APTT；于第7天取血由血液流变分析仪器LG-R-80（北京世帝科学仪器有限公司）完成全血粘度、血浆粘度、红细胞聚集指数、红细胞变形能力检测；对纤溶活性的影响（优秀球蛋白溶解时间ELT）取家兔随18只随机分成3组，设空白对照组，丹芎抑凝饮根据服用中药剂量不同设高低两个剂量组，每组6只。各组按公斤体重灌胃给药给，每日一次，连续给药7天后，取血，加钙法测定ELT；同样方式，7天后取血应用比浊法测定5分钟内血小板最大聚集率，并计算对血小板的抑制率。 <WP=5> 结果：服用丹芎抑凝饮中药组的家兔，PT、APTT逐渐延长，于第3天时取血化验PT、APTT丹芎抑凝饮低高剂量组与空白组间比较无统计学差异(P>0.05)，而服用华法林组的家兔与其他三组相比较PT、APTT显著延长(P<0.05)。服药后第5天丹芎抑凝饮低高剂量组、华法林组与空白组间比较PT、APTT 均显著延长(P<0.05)。丹芎抑凝饮低高剂量组与华法林组无统计学差异(P>.05)。服药后第7天丹芎抑凝饮低高剂量组、华法林组与空白组间比较PT、APTT 均显著延长(P<0.01)。丹芎抑凝饮低高剂量组与华法林组无统计学差异(P>.05)。于第7天取血检测血液流变学的各项指标：华法林组虽然也可以降低血液粘度但在红细胞变形能力上与空白组对照，无统计学差别。丹芎抑凝饮低高剂量组则显示在改善血液流变学各项指标中优于华法林组(P<0.05)。主要表现在降低全血粘度、血浆粘度同时降低红细胞的聚集性，增强了红细胞的变形能力。对于血小板聚集率的比较：结果丹芎抑凝饮低高剂量组对家兔的血小板最大聚集率分别为33.29±4.72%，25.57±3.27 %与空白组比较67.32±5.21%显示明显的抑制血小板聚集的作用(P<0.01)。丹芎抑凝饮对优球蛋白溶解时间低高剂量组118.7±12.6min，109.4±9.8min与空白组145.5±13.9min做对照显著降低(P<0.01)。结论：实验证明中药组方丹芎抑凝饮可以使PT、APTT显著延长，对凝血过程中存在的内源性和外源性两条途径都存在干预作用。丹芎抑凝饮可显著改善血液流变学各项指标全血粘度、血浆粘度、红细胞聚集指数、红细胞变形指数，并能够显著抑制血小板的聚集。说明其有调节血液的流变性，改善血液的“浓、粘、凝、聚”的倾向等作用，这与祖<WP=6>国医学所记载的破血逐瘀的理论相一致。丹芎抑凝饮对优球蛋白溶解时间与空白组作对照显著缩短(P<0.01)，其抗凝作用还与增强纤溶酶的活性有关。在丹芎抑凝饮中还包含了多种补益心气的中药党参、黄芪、白术、甘草、当归、白芍等，补气药虽对凝血及纤溶活性无直接影响；但能对活血药起到协同或增强作用。总之丹芎抑凝饮能够显著延长PT、APTT与华法林相当，在改善血液流变学全血粘度、血浆粘度、红细胞聚集指数、红细胞变形指数方面优于华法更多还原

【Abstract】 Objective: The task to prevent embolism after heart valve repalcement is always paid more attention all the while.Thrombus is induced by boring normal mechanism of blood coagalation and making some blood cell and protein actived.At last the thrombus of platelet-fibrin is formed.It is an complex proedss concluding so many kind of cell and metabolic channel and it has very close realation with hemorrheology. The drug of anti-vitaminK and anti-platele such as warfarin and asprin are applied in clinic.But they all have some side effects,for example, haemorrhage was easily brought on by warfarin. It is disputed if warfarin induces oaf at gestation. Furthermore the platele which is the main component of thrombus is not restrained by warfarin. Asprin results in a series of side effects of alimentary canal such as hemorrhage, canker,etc .Lately along with the study of salvia milliorhiza and ligusticum wallichii franch in-depth evidence for they do good to cardiovascular system become more and more.It can prevent thormbus through restraining platelet assembling. It is said that thrombus has relation with fettle of platelet assembling by <WP=8>Chinese iatrology.And that huoxuehuayu could restain platelet assembling, improve blood circulation and restrain platelet assembling. We supprose to select some Cinese medical herbs which has the effect of anticoafalation and cardioqi-nourishing technique. That we could make Danxiong Yiningyin (DX).Through the animal experiment choose some parameter which could reflect the anticoagalation and hemorrheology.We observe the effect of Danxiong Yiningyin in comparsion with warfarin in order to provide experimental data for the development and application of the two drugs in clinic .Methods:Choose pure bred twenty-four rabbits (2.2± 0.5kg).Divide them into four groups at radom. Every group has six rabbit.The four group include Danxiong Yiningyin low high group warfarin group and control group. The Chinese medical herbs of the root of red rooted salvia, chuanxiong, honghua,etc, provided by Hebei medical material company. Then make it into hydromel.Warfarin was made into power and mixed pured water into solution.Accroding to the weighth each rabbit take the drugs every day. Take the blood and then examine the PT,APTT at third, fifth, seventh day by appartus ACL-200(America backman).Examine the hemorrheologic at the seventh day by appartus LG-R-80 automatic blood analyzer（Beijing shidi company）.Examine the rate of platelet assembling max and ELT at the seventh day too. All data was tested with spss10.0 software. Numberical variable data were wxpressed mean( stand deviation.P value<0.05 was considered <WP=9>statistically signifiant difference. Result: Results showed that Dxiong Yiningyin could significantly prolong PT,APTT in rabbit which take it.The third day the PT,APTT of Dxiong Yiningyin low and high group were simliar with control group.No significantly different- ce(P>0.05)showed.but That compared with warfarin group, has significantly difference(P<0.05).At fifth day the Dxiong Yiningyin low and high group.No significant difference has found in two Chinese medical herbs(P>0.05). Compared with control group It has significant difference(P<0.05).Compare with warfarin group no significant difference was observed(P>0.05).At the seventh day no significant difference has found in two Chinese medical herbs(P>0.05).Compared with control group It has significant difference(P<0.05). Compare with warfarin group, no significant difference was observed(P>0.05).Take blood to examine the hemorrheologic parameters. Whole blood viscosity, plasm viscosity and erythrocyte deformed index lowered obviously as compared with warfarin group(P<0.05). The platele Amax in the DX group was 33.29±4.72%, 25.57±3.27 % and that Compare with control group significant difference was observed(P<0.05) in ELT.Conclousion: Through the animal experiment DX could significantly prolong PT,APTT in rabbit.It illuminates that DX interfere with endogenesis and exterior approach in cruor process. DX had a mor更多还原