中枢神经系统A1型星形胶质细胞通过C3/C3aR调控神经元-胶质细胞对话参与术后急性疼痛向慢性疼痛转化的机制研究

中枢神经系统A1型星形胶质细胞极化可能在术后急性疼痛向慢性疼痛的转化中发挥关键作用。前期研究发现，术后急性疼痛与慢性疼痛有关，而星形胶质细胞在术后7~21 d持续活化；但关于星形胶质细胞极化类型，及其对术后慢性疼痛转化的作用尚未阐明。此次研究中我们提出，术后急性疼痛期，中枢神经系统星形胶质细胞内活化的NF-κB通过上调C3使细胞极化为A1型；A1型通过C3再作用于小胶质细胞和神经突触C3aR，可促进小胶质细胞向促炎M1型转化、降低其吞噬修复能力，并调控突触重塑，最终促使术后疼痛由急性向慢性转化。研究拟应用Il1α−/−Tnf−/−C1qα−/−敲除鼠、多种特异性敲低腺病毒，结合膜片钳、单细胞微流体高通量qPCR等生物技术，探讨中枢神经系统A1型在术后急性疼痛向慢性疼痛转化中的关键作用，及C3/C3aR对小胶质细胞和神经突触的调控，为今后靶向干预术后慢性疼痛的产生提供新思路和理论基础。

The reactive astrocytes in the CNS are promised to mediate the transition from acute to chronic postoperative pain. Our previous studies have found that acute pain could predict chronic ones, and astrocytes were activated from postoperative day 7 to 21. But it remains to be elucidated about the phenotype, function and modulation of reactive astrocytes in the transition period. In this study, we propose that, the astrocytes are polarized into A1 phenotype by activating NF-κB pathway to upregulate C3 expression after surgery. The C3 then combine with C3aR in the microglial and synapsis, which polarizing the microglial into M1 phenotype, decreasing its phagocytosis and modulating synaptic plasticity, finally promoting acute postoperative pain developed into chronic one. We plan to use Il1α−/−Tnf−/−C1qα−/− knockout rats, several cell-specific knockdown adenovirus, combine with biological techniques like patch clamp, single-cell microfluidic qPCR to study the function and modulation of A1 astrocytes in the transition period. By targeting inhibition of the transition of chronic postoperative pain, our study could provide new idea and theoretical basis for future clinical strategies.