创新背景

缺血性脑卒中是指由于脑的供血动脉（颈动脉和椎动脉）狭窄或闭塞、脑供血不足导致的脑组织坏死的总称。缺血性脑卒中发病机制复杂，发病率高、病死性高、致残率高，开发相应治疗手段对于医学发展意义重大。

创新过程

脑卒中是脑血管循环障碍引起的疾病，分为缺血性脑卒中和出血性脑卒中，缺血性脑卒中占脑卒中的80%以上。缺血性脑卒中发病机制复杂，根据近年的研究，缺血性脑卒中发病与血栓性炎症息息相关。血栓性炎症由“接触—激肽”系统主导发生，其中最重要的两个成员是十二因子和血浆激肽释放酶。

治疗缺血性脑卒中可以追本溯源，抑制血栓性炎症的发生。从功能上抑制十二因子和激肽释放酶，可有效抑制缺血性脑卒中发病过程中血栓性炎症发生，从而抑制缺血性脑卒中发病。2022年4月，中国科学院昆明动物研究所赖仞研究员带领小组与多伦多大学倪合宇教授等人合作研究的活性多肽抑制缺血性脑卒中发病的成果发表在著名国际期刊《细胞和分子生命科学》上。

研究根据十二因子和激肽释放酶的作用，寻找专门抑制其的多肽，最终在山蛭中发现目标。蛭类是一种传统中药，《本草纲目》介绍了蛭类在抗凝血作用。2005年，欧洲正式批准蛭类疗法为合法的治疗手段。肽是两个或两个以上的氨基酸以肽键相连的化合物，对人体生理机能起重要作用。具有活性的多肽称为活性肽，又称生物活性肽或生物活性多肽。

研究从森林山蛭中鉴定了一个活性多肽，发现该多肽对于抑制激肽释放酶和十二因子的活性具有专一性，起作用的抑制常数分别为1.79纳米和2.98微米，有助于治疗短暂性缺血性脑卒中和永久性缺血性脑卒中有显著作用。同时，多肽在体内对于抗血栓的形成也具有积极作用。并且，该多肽没有溶血及细胞毒性，也没有出血风险，具备显著的候选药物开发特征。

利用活性多肽治疗缺血性脑卒中，是反向治疗的创新医学方式，可以开拓医疗思维和方法，促进医疗追本溯源，从源头寻找最恰当的针对性疾病治疗方法。

创新关键点

从山蛭中提取多肽，追本溯源反向利用活性多肽治疗缺血性脑卒中。

Treatment of ischemic stroke with active polypeptides

Stroke is a disease caused by cerebrovascular circulation disorders, which are divided into ischemic stroke and hemorrhagic stroke, and ischemic stroke accounts for more than 80% of stroke. The pathogenesis of ischemic stroke is complex, and according to recent studies, the onset of ischemic stroke is closely related to thrombotic inflammation. Thrombotic inflammation occurs predominantly by the "contact-kinin" system, the two most important members of which are factor twelve and plasma kinin-releasing enzyme.
Treatment of ischemic stroke can be traced back to the source and inhibit the occurrence of thrombotic inflammation. Functional inhibition of factor 12 and kallikrein can effectively inhibit the occurrence of thrombotic inflammation during the onset of ischemic stroke, thereby inhibiting the onset of ischemic stroke. In April 2022, the results of the active peptide inhibition of ischemic stroke disease in collaboration with Professor Ni Heyu of the University of Toronto led by researcher Lai Ling of the Kunming Institute of Zoology of the Chinese Academy of Sciences were published in the famous international journal "Cell and Molecular Life Science".
Based on the action of factors dodecagon and kallikrein, studies look for polypeptides that specifically inhibit them, eventually finding targets in leeches. Leeches are a traditional Chinese medicine, and the Compendium of Materia Medica introduces the anticoagulant effects of leeches. In 2005, Europe officially approved leech therapy as a legal treatment. Peptides are compounds in which two or more amino acids are bonded together and play an important role in human physiology. A peptide with activity is called an active peptide, also known as a bioactive peptide or a bioactive polypeptide.
An active polypeptide was identified from forest leeches and found that the polypeptide has a specific effect on inhibiting the activity of kallikrein and factor duode, and the inhibition constants that play a role are 1.79 nanometers and 2.98 microns, respectively, which are helpful in the treatment of transient ischemic stroke and permanent ischemic stroke. At the same time, peptides also have a positive effect on the formation of anti-thrombosis in the body. Moreover, the polypeptide has no hemolysis, cytotoxicity, and no bleeding risk, and has significant drug candidate development characteristics.
The use of active peptides to treat ischemic stroke is an innovative medical method of reverse treatment, which can open up medical thinking and methods, promote medical tracing, and find the most appropriate treatment methods for diseases from the source.