阿司匹林广泛应用于血栓栓塞性疾病的防治，但即使小剂量阿司匹林也可增加消化道损伤风险。PPI是治疗阿司匹林致消化道损伤的首选药物，但近年来多项研究已提示长期服用PPI可能会带来安全性问题，值得临床关注。我们前期研究发现脂肪间充质干细胞（ADMSC）可促进NSAID相关性胃溃疡早期愈合，且该过程不依赖干细胞在体内的定植和分化，推测其旁分泌活性可能起着更加关键的作用，其中可能涉及外泌体。本课题将探索利用ADMSC来源的外泌体治疗阿司匹林相关性胃粘膜损伤的可能性及作用机制。我们将通过体内外实验研究外泌体对阿司匹林干预后细胞活力、增殖、凋亡、氧化应激、迁移及血管形成的影响。机制上，我们将关注外泌体装载miR-23a-3p传递至受体细胞，通过靶向PTEN活化PI3K/Akt通路而调控细胞活动。本项目的研究成果将为临床防治阿司匹林致消化道粘膜损伤提供新思路，具有一定的临床意义和转化前景。

Aspirin is widely prescribed for thromboembolic disorders, but even low dosage of aspirin can increase the risk of gastrointestinal damage. PPI is the drug of choice for the treatment of aspirin-induced gastrointestinal damage, but studies in recent years have showed that long-term use of PPI may bring safety issues that deserve clinical attention. Our previous study has demonstrated that adipose-derived mesenchymal stem cells (ADMSCs) can promote the early healing of NSAID-related gastric ulcers, and this process does not depend on the engraftment and differentiation of stem cells in vivo, suggesting the paracrine activity of stem cells might be much more important, in which it might involve the role of exosomes. Therefore, our current project will explore the possibility of using ADMSC-derived exosomes for the treatment of aspirin-related gastric mucosal injury. We will study the impact of exosomes on the cell viability, proliferation, apoptosis, oxidative stress, migration and angiogenesis after aspirin intervention both in vivo and in vitro. Mechanistically, we will explore the process for exosomes to deliver the encapsulated miR-23a-3p to the receipt cells and to regulate the activation of PI3K/Akt pathway through targeting PTEN, thereby modulating cell activity. Our results may provide new strategy for clinical prevention and treatment of aspirin-induced gastrointestinal mucosal injury, which has certain clinical significance and prospects for translation.