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新型水蛭素嵌合抗栓剂的构建表达与功能研究
引用本文:牛晋阳,董春娜,靳继德,石炳兴,吴祖泽.新型水蛭素嵌合抗栓剂的构建表达与功能研究[J].中国生物工程杂志,2006,26(4):36-39.
作者姓名:牛晋阳  董春娜  靳继德  石炳兴  吴祖泽
作者单位:军事医学科学院全军实验血液学重点实验室 军事医学科学院全军实验血液学重点实验室 军事医学科学院全军实验血液学重点实验室 军事医学科学院全军实验血液学重点实验室 军事医学科学院全军实验血液学重点实验室
摘    要:水蛭素(Hirudin,HV)作为新一代抗凝剂,它是目前已知最强的天然凝血酶抑制剂,并有望在临床上完全取代肝素。虽然水蛭素有许多优点,但出血倾向是其在临床应用上的主要副作用。目前尚没有好的解决办法。针对水蛭素在临床应用中所出现的这个问题,依据血栓形成的生理生化机制,构建出了含FXa识别序列水蛭素嵌合抗栓剂,来降低水蛭素在非血栓部位的活性从而减小出血的危险。小鼠尾部血栓模型实验表明:此新型嵌合抗栓剂能在不减少水蛭素抗凝血活性的同时,又能大幅度地降低出血副作用。具有非常重要的临床意义。

关 键 词:水蛭素  出血副作用  
收稿时间:2005-12-05
修稿时间:2005年12月5日

Design and functional investigation of a novel anti-coagulative fusion protein by hirudin with a recognizing sequence of FXa
NIU Jin-yang,DONG Chun-na,JIN Ji-de,SHI Bing-xing,WU Zu-ze.Design and functional investigation of a novel anti-coagulative fusion protein by hirudin with a recognizing sequence of FXa[J].China Biotechnology,2006,26(4):36-39.
Authors:NIU Jin-yang  DONG Chun-na  JIN Ji-de  SHI Bing-xing  WU Zu-ze
Abstract:Hirudin (HV) is known as the most potent and specific inhibitor of thrombin. Although hirudin has many advantages , it has the bleeding side effect and this is the great shortage of hiudin for clinical application. In order to alleviate bleeding side effect of hirudin, fusion protein, named as FHV (fusion hirudin linked with FXa recognition peptide) was designed. The fusion protein gene ( fhv) was cloned into plasmid pPIC9K. FHV engineered Pichia pastoris containing high copies was chosen for fermentation and purification at 30 L fermentor scale, finally, FHV with purity of above 97% was obtained. To investigate the function of FHV in vivo, mouse tail thrombosis model was used. In the mice thrombus tail model induced by carrageenan, FHV decreased the length of tail thrombus significantly, similar to that of HV control, and had no obvious effects on the TT, PT and APTT. In conclusion, FHV is constructed and expressed in yeast. FHV fusion proteins is obtained by fermentation and purification. FHV has antithrombotic effects not influencing IT, PT and APTT after administration immediately in animal models. Therefore, FHV is a promising anticoagulant and antithrombotic drug.
Keywords:FXa
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