水蛭素融合蛋白探究进展.docVIP

水蛭素融合蛋白探究进展 　【摘要】 水蛭素是一种高效特异的凝血酶抑制剂，临床上用于血栓病的预防和治疗，但它半衰期短、出血副作用强和功能单一。近年来，通过把水蛭素与某些功能蛋白融合表达来解决这些问题，得到的融合蛋白或在体内延长水蛭素的半衰期，或降低其出血副作用，或带来新的功能，如：溶栓、抑制血小板凝集、特异寻靶等。本文对近年来国内外水蛭素融合蛋白研究状况进行综述。 【关键词】 水蛭素 融合蛋白 抗凝 血栓形成 Research Progress in Hirudin Fusion Protein ——Review Abstract Natural hirudin extracted from the secretion of medical leech salivary gland is a singlechain peptide containing 65 aminoacid residues with molecular weight of 7000 D, and exists in three isomers of HV1, HV2 and HV3. Hirudin possesses three disulfide bridges forming the structure of core cyclic peptides, which binds to the catalytic site of thrombin so as to inhibit the catalysis of thrombin. Its cterminus rich in acidic aminoacid residues possesses hydrophilicity, and is free on the molecular surface, and can bind with fibrin recognition site of hirudin. The minimal segment of 12-16 Cterminal acidic residues keeps the minimal activity of antithrombosis. Thus, hirudin, as a potent and specific inhibitor of thrombin, can be used to protect from and to treat clinically thrombosis. As it has some disadvantages such as short halflife, bleeding sideeffect and monofunction, and so on, hirudin has been fused with some other functional proteins in recent years. The obtained fusion proteins can prolong the half life of hirudin, or relieve it bleeding side effect, or bring new functions, such as thrombolysis, inhibiting the platelet aggregation, targething specifically. The research progress in hirudin fusion protein was summarized in this review. Key words hirudin； fusion protein；anticoagulation； thrombosis 当今心血管疾病已成为危害人类健康的头号敌人，其中血栓的形成是引起心脑血管疾病的重要原因。水蛭素是近年来研制开发的新一代抗凝蛋白药物，被用于血栓病的预防和治疗，其效果明显优于肝素，而又无肝素诱导的血小板减少症［1］。但是水蛭素作为一种小分子蛋白药物，同样具有在体内代谢快，半衰期短的缺点,通过把水蛭素与辅助多肽融合表达，就可以使水蛭素在人体内缓慢释放，延长半衰期；水蛭素只有抗凝作用，而没有溶栓功能，通过与其他溶栓蛋白融合表达，就可以得到抗凝溶栓双功能蛋白药物， 将更有效的溶解血凝块并抑制新血栓的形成；水蛭素在体内有广泛的抑制凝血酶作用，当水蛭素的剂量大于抗凝所需的剂量时，就会发生明显的出血现象，通过与纤维蛋白特异抗体融合，就使得水蛭素在血栓部位富集，有效的发挥抗凝功能，从而避免全身的出血副作用。另外，水蛭素与其他抗凝成分结合，就会从多个途径阻断血栓的形成，更高效的起到抗栓效果。近年来，许多人将