食管ESD术后狭窄是亟待解决的临床问题。目前食管ESD术后狭窄的预防措施效果均不理想且存在诸多问题，积极探索食管ESD术后狭窄的发生机制，开发可用于临床预防食管狭窄的新方法和新技术具有重要的临床意义。目前认为，食管ESD术后创面迁延的炎症反应是导致狭窄的重要原因。我们前期研究发现TLR4介导的成纤维细胞源性外泌体可能在食管ESD术后炎症微环境的调控中发挥关键作用，而新型取向碳纳米管可以通过诱导细胞行为负向调控TLR4，从而预防食管ESD术后狭窄。本项目在前期研究基础上，运用细胞学实验探索TLR4介导成纤维细胞外泌体中关键分子的调控机制，并运用体外和体内实验验证TLR4介导的成纤维细胞源性外泌体对炎症微环境的具体作用，最终通过动物模型和临床实验对取向碳纳米管预防食管ESD术后狭窄的安全性和有效性进行初步论证。期待通过本项目丰富食管ESD术后狭窄发生机制，为其预防提供安全可靠的新材料。

Esophageal stricture (ES) after endoscopic submucosal dissection (ESD) is one of urgent clinical problems that call for resolutions. Currently, the approaches in the prevention of post-ESD ES are far from satisfactory and cause a series of problems. It possesses great significance to investigate the mechanisms of post-ESD ES and develop new methods or techniques that can be clinically used to prevent post-ESD ES. It is well recognized that the excessive and persistent inflammation reaction at the wound site after ESD is the main reason causing ES. We have previously observed that fibroblast-derived exosomes mediated by toll-like receptor 4 (TLR4) may play a key role in the regulation of the inflammation microenvironment after ESD, and novel aligned carbon nanotubes (ACNTs) could downregulate TLR4 by inducing cell behavior and ultimately prevent post-ESD ES. The present project will continue to investigate the intracellular mechanisms of TLR4 in the regulation of key molecules contained in fibroblast-derived exosomes using human esophageal fibroblast cell line. The specific effects of fibroblast-derived exosomes on the inflammation microenvironment will be tested and verified both in vitro and in vivo. Finally, the safety and efficacy of ACNTs in the prevention of post-ESD ES will be examined on the porcine model and clinical patients. We hope this project will enrich the mechanisms of post-ESD ES and provide a reliable material and technique in the prophylaxis of post-ESD ES.