重组水蛭素的抗血栓形成作用及其机制  

Antithrombotic effects of recombinant hirudin in mice and its mechanism

作　　者：曹文理[1] 李菁[2] CAO Wen-li;LI JING(Department of Respiratory and Intensive Care Unit;Department of Prevention and Health Care,Affiliated Hospital of Logistics College of Chinese People＇s Armed Police Forces,Tianjin 300162,China)

机构地区：[1]武警后勤学院附属医院呼吸和重症医学科 [2]武警后勤学院附属医院预防保健科,天津300162

出　　处：《中国应用生理学杂志》2018年第4期371-374,共4页Chinese Journal of Applied Physiology

基　　金：武警后勤学院附属医院种子基金(FYM201612)

摘　　要：目的:研究重组水蛭素抗血栓形成的作用及机制。方法:将60只雄性昆明小鼠随机分为对照组、模型组、阿司匹林组和重组水蛭素低、中、高剂量组(n=10)。除对照组外,其余各组小鼠分别腹腔注射角叉菜胶2.5mg/kg,诱发小鼠尾部血栓形成。注射角叉菜胶前24 h、0.5 h和注射后24 h,阿司匹林组小鼠分别腹腔注射阿司匹林25 mg/kg,重组水蛭素低、中、高剂量组小鼠分别腹腔注射0.05、0.1、0.2 mg/kg重组水蛭素,对照组和模型组小鼠分别腹腔注射等体积生理盐水。注射角叉菜胶后48 h,观察小鼠黑尾长度并计算黑尾发生率;检测血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活物抑制因子-1(PAI-1)、6-酮-前列腺素F1α(6-keto-PGF1α)、血栓恶烷B2 (TXB2)水平。结果:与对照组比较,模型组小鼠尾部形成血栓;血浆PT明显缩短(P<0.01),PAI-1、TXB2水平明显升高(P<0.01),t-PA、6-keto-PGF1α水平明显降低(P<0.01)。与模型组比较,重组水蛭素低、中、高剂量组和阿司匹林组小鼠尾部血栓长度明显缩短(P <0. 05或P <0.01),PT明显延长(P<0.01),PAI-1、TXB2水平明显降低(P<0.01),t-PA、6-keto-PGF1α水平明显升高(P<0.01)。与阿司匹林组比较,重组水蛭素低剂量组小鼠尾部血栓长度明显增加(P<0.05),PT明显缩短(P<0.01),PAI-1、TXB2水平明显升高(P<0.01);重组水蛭素低、中剂量组6-keto-PGF1α水平明显降低(P<0.01,P<0.05);重组水蛭素中剂量组PAI-1、TXB2水平明显升高(P<0.01,P<0.05)。结论:重组水蛭素有明显抗血栓形成作用,其机制可能与影响外源性凝血系统、促进纤溶功能有关。Objective： To investigate the antithrombotic effects of recombinant hirudin and its mechanism. Methods： Sixty male Kunming mice were randomly divided into 6 group（ n = 10） ： control group,model group,aspirin（ 25 mg/kg） group,recombinant hirudinlow,middle and high dose（ 0.05,0.1,0.2 mg/kg） groups.Except mice in control group,2.5 mg/kg carrageenan was injected intraperitoneallyto mice in the other groups to produce thrombosis on the mice tail. The mice in aspirin group were administrated intraperitoneally 25 mg/kg aspirin,the mice in recombinant hirudinlow,middle and high dose groups were administrated intraperitoneally0.05,0.1,0.2 mg/kg combinanthirudin,the mice in control group and model group were administrated intraperitoneallynormal saline at the same volume respectively at 24 h,0.5 h before injecting carrageenan and 24 h after injecting carrageenan. The black tail length of mice and the incidence of black tail were observed at 48 h after injection of carrageenan; prothrombin time（ PT）,activated partial thromboplastin time（ APTT）,tissue plasminogen activator（ t-PA）,type-1 plasminogen activator inhibitor（ PAI-1）,6-keto-PGF1α,and thromboxane B2（ TXB2） level in mice plasma were determined. Results： As compared with control group,the mice in model group presented tail thrombosis; PT level in plasma was significantly shortened（ P〈0.01）,PAI-1 and TXB2 levels in plasma were significantly increased（ P〈0.01）,while the t-PA and 6-keto-PGF1α levels in plasma in model group were significantly decreased（ P〈0.01）. As compared with model group,the thrombus length in the tail was significantly shortened（ P〈0.05,P〈0.01）,PT level was obviously prolonged（ P〈0.01）,and the plasma levels of PAI-1 and TXB2 were significantly decreased（ P〈0.01）,while the plasma levels of t-PA and 6-keto-PGF1α were significantly increased（ P〈0.01） in the mice of recombinant hirudin low dose,middle dose,high dose groups and aspirin group. As compared with aspirin gro

关 键 词：重组水蛭素 角叉菜胶 血栓 凝血 小鼠 

分 类 号：R285.5[医药卫生—中药学]