装载胸腺素β4的间充质干细胞外泌体在自身免疫性干眼中的作用及机制研究

自身免疫性干眼是一种慢性难治性干眼类型，严重影响人们的视力和生活质量，目前临床上尚缺乏有效的治疗措施。胸腺素β4（Tβ4）是一类具有抗炎和免疫调节功能的多肽类药物，但其在干燥综合征相关干眼中的作用及机制尚未见报道。我们前期研究显示间充质干细胞来源的外泌体（MSC-exo）能缓解兔自身免疫性干眼的临床症状。近期研究显示MSC-exo作为天然的药物载体可以延长多肽类药物在体内的作用时间，增强其治疗效果。结合前期研究和最新进展，本课题将构建装载Tβ4的MSC-exo复合制剂，提高Tβ4体内的稳定性及生物利用度。利用兔泪腺特异性激活的自体外周血淋巴细胞诱导的兔干眼模型，研究MSC-exo-Tβ4在不同的给药模式和作用时机下对自身免疫性干眼发生发展的影响，并通过一系列体内外实验探索其作用机制，为MSC-exo-Tβ4干眼临床应用转化提供科学依据，以期为自身免疫性干眼的防治提供新型生物复合制剂。

Autoimmune dry eye is one of clinical chronic and refractory ocular surface disorders, substantially affecting vision and quality of life, and there is no radical treatment for it at present. Thymosin β4 (Tβ4) is a polypeptide drug with anti-inflammatory and immunoregulatory functions. However, the role and mechanisms of Tβ4 in Sjögren’s syndrome-related autoimmune dry eye have not been reported. Our preliminary experimental results have shown that mesenchymal stem cells derived exosomes (MSC-exo) treatment effectively ameliorates rabbit autoimmune dacryoadenitis. Recent study showed that MSC-exo, as a natural drug-delivery vehicle, can extend the in vivo action time of peptide drugs and enhance their therapeutic effects. In this study, Tβ4 will be incorporated into MSC-exo in order to improve its stability and tissue bioavailability. We will further explore the therapeutic effects and underlying mechanisms of Tβ4-loaded MSC-exo in rabbit autoimmune dry eye induced by transfer of antigen-specific peripheral blood lymphocytes. This study will provide the scientific basis for clinical application and translation of MSC-exo-Tβ4 in autoimmune dry eye treatment.