原发性干燥综合征（pSS）相关干眼的发病机制核心是泪腺进行性损伤，尚缺乏有效的病因治疗和靶器官保护措施。损伤后异常凋亡的泪腺上皮细胞（LGECs）可激活自身免疫系统、加重炎症反应及靶器官损伤，形成“损伤-炎症-损伤”恶性循环；而线粒体凋亡途径是LGECs凋亡的重要途径。我们前期研究发现脂肪干细胞外泌体（ADSC）可显著增加pSS小鼠泪液分泌，减少LGECs凋亡并降低PDCD4表达，而PDCD4参与调控线粒体凋亡途径。此外，根据microRNA基因芯片分析结果，我们推测ADSC外泌体可能通过递送miR-21-5p作用PDCD4定向调控LGECs线粒体途径凋亡的激活，实现pSS泪腺损伤保护，但机制细节尚待阐明。本项目拟利用荧光示踪、miRNA拟物、生物信息分析等技术方法，从细胞及动物层面明确ADSC外泌体调控LGECs凋亡保护pSS泪腺损伤的作用并探究机制，为pSS相关干眼的治疗提供新的途径。

Patients with primary Sjögren's syndrome (pSS)-related dry eye have severe symptom due to progressive lacrimal gland injury, which lacking of effective etiological treatment or protection for target organ. Recent studies indicated that apoptotic lacrimal gland epithelial cells (LGECs) could activate immune responses against remained LGECs, accelerate inflammation and induce further injury of target organs, which sets up a vicious cycle of “injury-inflammation-injury” in pSS lacrimal gland. Mitochondrial apoptotic pathway plays an important role in lacrimal gland injury in pSS patients. Our previous research validated that adipose-stem-cell derived exosomes (ADSC-exo) significantly increased tear production in pSS mouse, attenuated cell apoptosis and decreased the expression of PDCD4, which is involved in regulating mitochondrial apoptotic pathway in LGECs of pSS mouse. Further sequencing results have led to our hypothesis that ADSC-exo might protect lacrimal gland in pSS-related dry eye by regulating mitochondria apoptotic pathway via carrying microRNA-21-5p targeting PDCD4. In this study, the protecting role and the regulatory mechanism of ADSC-exo towards lacrimal gland injury will be investigated by fluorescent staining tracer technique，antago/agomir technique, bioinformatics analysis and molecular biological methods both in vitro and in vivo. The study will provide a theoretical basis for development of ADSC-exo dependent biotherapy, and provide a new target and intervention strategy for the treatment of pSS-related dry eye.