抗炎药已成为我国动物临床仅次于抗感染药的第二大类常用药，常配合其他药物治疗各类因素引起的发热及病毒性疾病。目前，我国现有动物用抗炎药品种单一、副作用明显，故而研发抗炎活性强、毒副作用小、半衰期长的新型动物专用抗炎药迫在眉睫。项目组已成功在构建的家蝇幼虫抑制性消减杂交文库中筛选获得一个新型丝氨酸蛋白酶抑制剂编码基因（MDSPI16），该基因编码的蛋白具有强抗炎活性，但其分子量较大，临床应用易产生免疫反应。为此，本研究将采用分子生物信息学技术，通过动力学模拟确定重要活性口袋和残基，在不影响其抗炎活性的前提下构建截短蛋白；采用不同链长、不同分子量的聚乙二醇对其进行修饰，构建不同构象的修饰文库；进而在对单偶联产物进行纯化和鉴定的基础上确定其不同单偶联产物对弹性蛋白酶的抑制活性，并通过构建中性粒细胞炎症模型和小鼠肺损伤模型对其抗炎活性进行检测。上述研究成果将为新型抗炎药物的研发奠定基础。

Anti-inflammatory drugs have become the second common medicine category only to anti-infectives in our country’s animal clinic and often cooperate with other drugs to treat the fever and viral diseases caused by various factors. At present, the existing anti-inflammatory drugs for animal not only have very single varieties but significant side effects. Thus, it is of urgent need to develop a novel anti-inflammatory agent for animal with strong anti-inflammatory activity, long half-time and few side effects. Our project team has successfully selected a novel serine protease inhibitor coding gene（MDSPI16）from a housefly larvae suppression subtractive hybridization library constructed previously. The protein encoded by the MDSPI16 exerts strong anti-inflammatory activity but the bigger molecular weight makes it much prone to immune response. Hence, in this study, molecular dynamics simulation was performed to determine the active binding pockets and residues based on molecular bioinformatics; The truncated proteins under the premise of not impacting anti-inflammatory activity will be constructed; A modified library will be constructed by MDSPI16 modification using polyethylene glycol of various chain length and different molecular weight; The inhibitory activity of different MDSPI16 single conjugates to elastase will be measured by purifying and identifying single coupled products and the anti-inflammatory activity be further detected by establishment of neutrophil inflammation model and lung injury model of mice. The results above will lay the foundation for research and development of novel anti-inflammatory drugs.