富集miR-9的HUC-MSCs外泌体通过TLR4调控NLRP3炎症小体活化治疗IC/BPS疼痛的机制研究

膀胱疼痛是间质性膀胱炎/膀胱疼痛综合征（IC/BPS）的突出症状，严重影响患者生活质量。研究证实，神经胶质细胞中TLR4介导的NLRP3炎症小体的激活与慢性神经病理性损伤密切相关。申请人前期通过构建转基因小鼠IC/BPS模型发现，脊髓神经胶质细胞的活化在IC/BPS膀胱疼痛中发挥重要作用，且与TLR4介导的NLRP3活化后诱发的炎症反应密切相关；生物信息学与预实验结果显示，miR-9不仅靶向调控TLR4表达，且其下调参与了膀胱疼痛的发生，但miR-9是否可通过调控TLR4缓解膀胱疼痛及其分子机制尚不清楚。本项目拟以转基因小鼠IC/BPS模型为基础，阐明miR-9通过靶向神经胶质细胞TLR4调控NLRP3炎症小体活化在IC/BPS疼痛中的作用及分子机制，探讨通过富集microRNAs的HUC-MSCs源外泌体治疗IC/BPS疼痛的机制及可行性，以期为IC/BPS疼痛防治提供新的治疗方法及策略

Bladder pain is the most prominent symptom of interstitial cystitis/bladder pain syndrome (IC/BPS), which seriously affects the patients’ quality of life. Prior studies have suggested that the activation of TLR4-mediated NLRP3 inflammasome in neuroglia is closely related to chronic neuropathic injury. In the previous study, we found that the activation of TLR4-mediated NLRP3 inflammasome and its induced inflammatory response in neuroglia played a major role in bladder pain of transgenic IC/BPS mouse model. Combined with bioinformatics, literature reports and preliminary results, we found that decreased expression of miR-9 was closely related to chronic pain, and miR-9 had the potential binding site for TLR4, but their relationship and role in bladder pain of IC/BPS remain unclear. In the current study, on the basis of IC/BPS model, we use various techniques including bioinformatics, cell and molecular biology, and experimental zoology, to elucidate the role and molecular mechanism of TLR4 in regulating the activation of NLRP3 inflammasome in bladder pain of IC/BPS, and investigate the mechanism and feasibility of HUC-MSCs-derived exosomes enriched with microRNAs in the treatment of bladder pain of IC/BPS. This project can provide a new treatment method and strategy for the prevention and treatment of bladder pain of IC/BPS.