Ye Tianyu, Zhao Fang, Xiao Mingkang, Yin Jingjing, Ai Rui, Tang Lizhou, Liu Zichao, Huang Zuhao, Lin Gonghua
School of Life Sciences, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, Jinggangshan University, Ji'an 343009, China.
College of Life Sciences, Jiangxi Normal University, Nanchang 330022, China.
Biology (Basel). 2025 Jul 23;14(8):918. doi: 10.3390/biology14080918.
Thrombotic diseases represent a significant global health burden, particularly for middle-aged and elderly populations. Medicinal leeches, such as and , have been traditionally used for their anticoagulant properties. The genomes of these leeches each harbor three lefaxin genes, which are designated and , respectively. We conducted genomic and transcriptomic sequencing on wild populations of both species. Bioinformatics tools were employed to analyze intraspecific variation, molecular evolution, and protein structures. We expressed recombinant lefaxin proteins in and assessed their anticoagulant activities using in vitro coagulation assays. exhibited greater genetic diversity and stability, whereas showed higher expression levels and hydrophilicity. Both species exhibited purifying selection, indicating conserved function, and their lefaxin structures are similar to the archetypal lefaxin (UniProt No. P86681.1). lefaxins bound Factor Xa more effectively. lefaxins exhibited more robust anticoagulant activity in vitro compared to those from . , a non-hematophagous leech, shows potent anticoagulant activity through lefaxins, challenging traditional views on leech efficacy. This study underscores the potential of lefaxins as therapeutic targets for thrombotic diseases and highlights the need to reconsider the use of various leech species in medicine.
血栓性疾病是全球重大的健康负担，对中老年人群尤为如此。药用蚂蟥，如[蚂蟥种类1]和[蚂蟥种类2]，传统上因其抗凝血特性而被使用。这些蚂蟥的基因组各自含有三个类凝血酶原激活剂基因，分别命名为[基因名称1]、[基因名称2]和[基因名称3]。我们对这两个物种的野生种群进行了基因组和转录组测序。利用生物信息学工具分析种内变异、分子进化和蛋白质结构。我们在[表达系统]中表达重组类凝血酶原激活剂蛋白，并使用体外凝血试验评估其抗凝血活性。[蚂蟥种类1]表现出更大的遗传多样性和稳定性，而[蚂蟥种类2]显示出更高的表达水平和亲水性。两个物种都表现出纯化选择，表明功能保守，并且它们的类凝血酶原激活剂结构与原型类凝血酶原激活剂（UniProt编号P86681.1）相似。[蚂蟥种类1]的类凝血酶原激活剂与凝血因子Xa结合更有效。与[蚂蟥种类2]的类凝血酶原激活剂相比，[蚂蟥种类1]的类凝血酶原激活剂在体外表现出更强的抗凝血活性。[非吸血蚂蟥种类]通过类凝血酶原激活剂显示出强大的抗凝血活性，这挑战了关于蚂蟥功效的传统观点。这项研究强调了类凝血酶原激活剂作为血栓性疾病治疗靶点的潜力，并突出了重新考虑在医学中使用各种蚂蟥物种的必要性。
