circ_0049726/miR-6515-5p/NLRP3轴在椎间盘异常炎性反应中的作用及机制研究

椎间盘退变（IVDD）及其导致的腰痛严重影响人类健康，异常炎性反应为IVDD的重要因素。申请人前期研究发现炎性小体NLRP3(N3)可导致椎间盘异常炎性反应，炎性因子亦可调控环状RNA的表达，提示环状RNA及N3可能参与了IVDD及其导致的腰痛进程。预实验发现miR-6515-5p(miR-5p)可结合N3并抑制其表达，且生物信息学推测circ_0049726(c_6)与miR-5p存在大量竞争结合位点。据此我们推测：c_6通过海绵吸附作用拮抗miR-5p功能，miR-5p通过抑制N3表达及其继发的炎性反应减缓IVDD及其导致的腰痛发生。本项目拟在细胞及分子水平探讨及验证c_6拮抗miR-5p对N3的调控作用；同时在IVDD及疼痛动物模型中明确c_6/miR-5p/N3轴在异常炎性反应中的作用，本项目将为以c_6/miR-5p/N3轴为核心治疗IVDD及其导致的腰痛提供新的理论和实验基础。

Intervertebral disc degeneration (IVDD) and its associated low back pain seriously affect human health. Abnormal inflammatory response is an important factor of IVDD.The previous study of the applicant found that inflammatitis NLRP3(N3) can cause abnormal inflammatory action of intervertebral disc, and inflammatory factors can also regulate the expression of circular RNA, suggesting that circular RNA and N3 may be involved in the process of IVDD and its associated low back pain.Preliminary experiments found that miR-6515-5p (miR-5p) could bind to N3 and inhibit its expression, and bioinformatics speculated that circ_0049726(c_6) had a large number of competitive binding sites with miR-5p.Therefore, we speculated that c_6 antagonized the function of miR-5p by sponge adsorption, and miR-5p attenuates the occurrence of IVDD and its associated low back pain by inhibiting the expression of N3 and its secondary inflammatory response.This project intends to explore and verify the antagonistic role and mechanism of c_6 against the regulation of miR-5p on N3 at the cellular and molecular levels. At the same time, to clarifythe role of c_6/ miR-5p /N3 axis in the inflammatory response of abnormal intervertebral disc in the IVDD and pain animal models. This project will provide a new theoretical and experimental basis for the treatment of IVDD and its associated low back pain with c_6/ miR-5p /N3 axis.