基于Microglia-Astrocyte级联反应研究电针阻滞腰椎间盘突出症急性疼痛向慢性疼痛转化的外泌体miRNA机制

腰椎间盘突出症的慢性疼痛是疼痛领域需要攻克的难题。最近研究发现脊髓中小胶质细胞-星状胶质细胞级联反应参与急性疼痛向慢性疼痛的演变。我们前期研究提示：电针有阻滞腰椎间盘突出症急性疼痛向慢性疼痛演变的作用，且小胶质细胞和星状胶质细胞参与电针的上述作用，但二者级联通讯机制与电针作用的关系尚不清晰。外泌体携带的miRNA介导胶质细胞间通讯，调控基因转录。据此推测：小胶质细胞外泌体介导的miRNA调控星状胶质细胞的激活，促进慢性疼痛发展，电针通过调节小胶质细胞外泌体miRNA的表达，进而影响星状胶质细胞的活化和慢性疼痛的发展。拟探讨：⑴建立腰椎间盘突出症模型，进一步验证电针阻滞疼痛演变的作用；⑵电针干预的脊髓匀浆孵育激活小胶质细胞后，观测小胶质细胞外泌体对星状胶质作用；⑶高通量测序技术、生物信息学分析和体内外验证，寻找电针作用相关的外泌体miRNA。本研究有助于阐述电针阻滞疼痛演变的科学内涵。

How to alleviate chronic pain of lumbar disc herniation(LDH) is a serious medical problem.Recent studies have identified that spinal microglia and astrocytes,are of the utmost importance in the transition from acute pain to chronic pain.Our clinical practice and pre-experiments results showed that electroacupuncture can not only alleviated acute pain and chronic pain of lumbar disc herniation, but also prevent acute pain transforming to chronic pain.Spinal activated microglia and astrocytes are respectively play important roles in the early stage and mid-to-late stage pain of lumbar disc herniation,they participated in the effect of electroacupuncture analgesia.yet the mechanism(s) of signal transduction between microglia and astrocytes still need to be elucidated.Exosome-mediated miRNAs are involved in microglia-to-astrocyte communication,regulate gene expression in a post-transcriptional manner.We hypothesized that microglia derived exosomal miRNAs can regulate the activation of astrocytes and promote generation and maintenance of chronic pain. Electroacupuncture that regulates the expression of microglia derived exosomal miRNAs can affect activation of astrocytes and development of chronic pain.In this research we want to explore:⑴Set up the lumbar disc herniation model rats were induced by implantation of autologous nucleus pulposus, to verify the effect of electroacupuncture in inhibiting the transition of acute pain to chronic pain.⑵Study on the role of exosomal miRNA mediate microglia-astrocytes cascade via vitro glias cell culture.⑶High-throughput sequencing, bioinformatics analysis and in vivo and in vitro verification will be used to find exosomal miRNAs related therapeutic effect of electroacupuncture.The results of the current study will be helpful for understanding the mechanism of electroacupuncture in inhibit the transition of acute pain to chronic pain.