肿瘤坏死因子α的过度表达是导致脓毒症、类风湿性关节炎、克罗氏病（Croh's disease）、多发性硬化症等多种炎性及自身免疫性疾病的重要因素之一。如何有效清除血液中过量的TNF-α，是当前临床面临的重大疑难问题。临床用抗体类药物不仅价格昂贵，且存在潜在的安全风险。血液灌流技术可直接从血液中清除过多的TNF-α，为该类疾病的治疗提供了一种新的途径。本项目采用计算机模拟设计TNF-α 特异性亲和小分子配体；利用SPR、ITC等手段研究其与TNF-α相互作用机机制；通过对吸附剂载体孔径结构调控和分子手臂的调节，开发出对TNF-α具有特异性吸附作用的免疫吸附剂，进而通过动物实验系统评价该吸附剂对模型动物血液TNF-α的清除的有效性和安全性。项目的顺利实施，将为分子模拟技术在吸附剂配基设计以及血液灌流在治疗TNF-α相关疾病中的应用提供理论支持，具有重要的科学意义和临床价值。

The overexpression of tumor necrosis factor alpha is one of the important factors leading to multiple inflammatory and autoimmune diseases such as sepsis, rheumatoid arthritis, Crohn's disease and multiple sclerosis. How to effectively remove the excess TNF-α in the blood is a key problem in clinical. And the antibody drug used in clinical is not only expensive, but also has a potential safety risk. While, the hemoperfusion technology could directly remove the excessive TNF-α from the blood, and this may provide a new way for the treatment of related diseases. In this project, computer simulations will be used to design and screen TNF-α specific affinity ligands, and SPR and ITC method will be used to study their interaction effects and mechanisms. The effect of particle size and pore size of the matrix microspheres and the length of the spacer on the adsorption will be investigated by system adsorption experiment to finally select the best TNF-α immune adsorbent. And the eliminating efficiency of TNF-α and the biocompatibility of the adsorbent will be tested by animal experiments. The successful implementation of this project will provide theoretical support for molecular modeling in the design of protein ligands and the application of hemoperfusion in the treatment of TNF-α related diseases, which has important scientific significance and clinical value.