Cao Wen-Li, Li Jing
Department of Respiratory and Intensive Care Unit, Affiliated Hospital of Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China.
Department of Prevention and Health Care, Affiliated Hospital of Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2018 Apr 8;34(4):371-374. doi: 10.12047/j.cjap.5664.2018.085.
To investigate the antithrombotic effects of recombinant hirudin and its mechanism.
Sixty male Kunming mice were randomly divided into 6 group (=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 intraperitoneally 0.05, 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 48h 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.
As compared with control group, the mice in model group presented tail thrombosis; PT level in plasma was significantly shortened (<0.01), PAI-1 and TXB2levels in plasma were significantly increased (<0.01), while the t-PA and 6-keto-PGF1α levels in plasma in model group were significantly decreased (<0.01). As compared with model group, the thrombus length in the tail was significantly shortened (<0.05, <0.01), PT level was obviously prolonged (<0.01), and the plasma levels of PAI-1 and TXB2 were significantly decreased (<0.01), while the plasma levels of t-PA and 6-keto-PGF1α were significantly increased (<0.01)in the mice of recombinant hirudin low dose, middle dose, high dose groups and aspirin group. As compared with aspirin group, the thrombus length in the tail was significantly increased (<0.05), PT level was obviously shortened (<0.01), and the plasma levels of PAI-1 and TXB2 were significantly increased (<0.01)in the mice of recombinant hirudin low dose group; the plasma level of 6-keto-PGF1α was significantly decreased (<0.01, <0.05) in the mice of recombinant hirudin low dose and middle dose groups; the plasma levels of PAI-1 and TXB2 were significantly increased (<0.01, <0.05)in the mice of recombinant hirudin middle dose group.
The recombinant hirudin can fight against thrombosis, its antithrombotic mechanisms may be related to its influence on the exogenous coagulation system and the promotion of fibrinolysis function.
研究重组水蛭素的抗血栓作用及其机制。
将60只雄性昆明小鼠随机分为6组（每组10只）：对照组、模型组、阿司匹林（25mg/kg）组、重组水蛭素低、中、高剂量（0.05、0.1、0.2mg/kg）组。除对照组小鼠外，其他组小鼠腹腔注射2.5mg/kg角叉菜胶以在其尾部形成血栓。阿司匹林组小鼠腹腔注射25mg/kg阿司匹林，重组水蛭素低、中、高剂量组小鼠腹腔注射0.05、0.1、0.2mg/kg重组水蛭素，对照组和模型组小鼠在注射角叉菜胶前24h、注射角叉菜胶前0.5h及注射角叉菜胶后24h分别腹腔注射等体积的生理盐水。注射角叉菜胶48h后观察小鼠黑尾长度及黑尾发生率；测定小鼠血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、组织型纤溶酶原激活剂（t-PA）、1型纤溶酶原激活剂抑制剂（PAI-1）、6-酮-前列腺素F1α（6-keto-PGF1α）及血栓素B2（TXB2）水平。
与对照组相比，模型组小鼠出现尾部血栓形成；血浆PT水平显著缩短（P<0.01），血浆PAI-1和TXB2水平显著升高（P<0.01），而模型组血浆t-PA和6-keto-PGF1α水平显著降低（P<0.01）。与模型组相比，重组水蛭素低、中、高剂量组及阿司匹林组小鼠尾部血栓长度显著缩短（P<0.05，P<0.01），PT水平明显延长（P<0.01），血浆PAI-1和TXB2水平显著降低（P<0.01），而血浆t-PA和6-keto-PGF1α水平显著升高（P<0.01）。与阿司匹林组相比，重组水蛭素低剂量组小鼠尾部血栓长度显著增加（P<0.05），PT水平明显缩短（P<0.01），血浆PAI-1和TXB2水平显著升高（P<0.01）；重组水蛭素低剂量组和中剂量组小鼠血浆6-keto-PGF1α水平显著降低（P<0.01，P<0.05）；重组水蛭素中剂量组小鼠血浆PAI-1和TXB2水平显著升高（P<0.01，P<0.05）。
重组水蛭素具有抗血栓作用，其抗血栓机制可能与其对外源性凝血系统的影响及促进纤溶功能有关。
