宫颈过早成熟是自发性早产（sPTB）的主要原因，而过度炎性反应是sPTB宫颈早熟重要诱因。我们研究表明：激活胆碱能抗炎通路受体α7nAChR可下调sPTB大鼠炎性因子表达，并抑制宫颈成熟延长孕周，但其作用机制尚不明确。巨噬细胞极化表型转变引起的炎性微环境改变在组织重塑中发挥重要作用。预实验显示激活α7nAChR可抑制早产大鼠宫颈M1型巨噬细胞（促炎）产生，增加M2型巨噬细胞（抑炎）数目，抑制胶原蛋白表达和宫颈成熟，提示其可能通过调控巨噬细胞极化状态诱导宫颈成熟发生改变。本项目拟基于上述基础，（1）进一步明确α7nAChR对sPTB中巨噬细胞极化状态、炎性反应及宫颈成熟的作用；（2）通过药理学手段、基因操作激活和抑制α7nAChR，解析其调节巨噬细胞极化影响sPTB宫颈成熟的作用和分子机制；本研究将阐明α7nAChR调节sPTB中宫颈成熟的机制和关键分子，为寻找sPTB治疗靶点提供理论依据。

Cervical premature ripening is the primary cause of spontaneous preterm birth (sPTB), studies showed excessive inflammation played an important role in the process of cervical ripening in sPTB. Our previous study found, activating α7nAChR of cholinergic anti-inflammatory pathway could down-regulate the expression of inflammatory cytokines, inhibit cervical ripening and prolong gestation, however, the mechanism is still elusive. The phenotype switch of macrophage polarization contributes to the change of inflammatory microenvironment, which is vital for tissue remodeling. Preliminary result shows activating α7nAChR inhibits M1 macrophage (pro-inflammatory) and increases M2 (anti-inflammatory) macrophage in cervix of the sPTB rats, further decreases collagen expression and cervical ripening, indicating α7nAChR can regulate cervical ripening via mediating macrophage polarization. Based on the above mentioned facts, we further to characterize the roles of α7nAChR in the process of macrophage polarization, inflammatory change and cervical ripening in sPTB, to clarify the molecular mechanism of α7nAChR modulating macrophage polarization and regulating cervical ripening in sPTB via activating and inhibiting α7nAChR using pharmacological tool and gene manipulation. Our project will elucidate the mechanism and key factors of α7nAChR regulating cervical ripening in sPTB and provide theological basis for the search of new treatment target of sPTB.