改性水凝胶耦合MSC-exosomes源性miR-296-5P调控Cx3cl1治疗糖尿病ED的机制研究

骨髓间充质干细胞外泌体（MSC-exosomes）可治疗糖尿病勃起功能障碍（DMED），但机制不明，其在阴茎中的“突释”现象限制其疗效。前期通过外泌体测序及生信预测首次发现MSC-exosomes负载的miR-296-5P及其靶基因Cx3cl1可能促进血管再生及改善氧化应激，推测是其治疗DMED的作用机制。我们发明的具有抗氧化应激作用的新型改性水凝胶可耦合MSC-exosomes，限制其迅速流失，但其理化性质、最佳配比及作用时效仍待探索。本研究拟在前期研究基础上，应用mimics、体内外基因编辑及荧光示踪等技术，明确MSC-exosomes负载的miR-296-5P上调Cx3cl1分子机制，验证通过促进血管再生及抗氧化应激治疗DMED的作用及机制，并尝试最优化改性水凝胶与MSC-exosomes耦合条件，提高其治疗DMED的疗效，为MSC-exosomes治疗DMED提供理论和技术支撑。

Bone marrow mesenchymal stem cell derived exosomes (MSC-exosomes) shows potent in treating diabetes mellitus-induced erectile dysfunction (DMED), however, the mechanism remains unclear, besides， "sudden release" phenomenon in the penis limits its efficacy. It is first founded that MSC-exosomes loaded miR-296-5P and its target gene Cx3cl1 may promote vascular regeneration and improve oxidative stress based on our formal study of exosome sequencing and bioinformatic prediction, which is speculated it’s the mechanism of treatment for DMED. A new type of modified hydrogel was established by us. It shows anti-oxidative stress function and can be coupled with MSC-exosomes to limit their rapid loss, but its physical and chemical properties, optimal ratio and effect time are still need to be explored. This study intends to apply mimics, gene editing in vivo and in vitro, and fluorescence tracing on the basis of previous studies to clarify the molecular mechanism of upregulation of Cx3cl1 by miR-296-5P loaded in MSC-exosomes, clarifies its function and mechanism in improving angiogenesis and oxidative stress in DMED rats, tries to optimize the coupling conditions of modified hydrogel and MSC-exosomes to improve the therapeutic effect of DMED, and provides theoretical and technical support for MSC-exosomes treatment of DMED.