电针刺激调控胃肠道巨噬细胞聚集活化修复ICC的机制研究

Deletion or injury of ICC, which is the pathogenesis of a variety of gastrointestinal motility disorders, is closely related with macrophage gathering and activation. Our previous study found that electroacupuncture at ST36 could reduce the injury of ICC and repair the reticular structure of ICC, therefore increasing gastrointestinal motility. Whether electroacupuncture at ST36 could repair ICC damage through regulating the gathering and activation of macrophages in gastrointestinal tract and its mechanism need further investigation. On the basis of our previous study, this project intends to use GFP bone marrow transplantation model to explore whether electroacupuncture could influence macrophage gathering through regulating myeloid differentiation. It needs to examine whether electroacupuncture could regulate monocyte migration through MCP/CCR2 and downstream MAPK pathways, influence monocyte differentiation through M-CSF/c-FMS and intracellular JAK/STAT3 signaling pathway. We further to study whether electroacupuncture could have effects on macrophages activation by downregulating STAT1, NF-κB signaling pathways and upregulating JAK/STAT6 signaling pathway; and even much further to study the effect mechanism of macrophages activation on ICC by electroacupuncture. It needs to explore whether electroacupuncture could regulate inflammatory cytokines, reduce ICC apoptosis and relieve ICC oxidative stress injury.The above studies may provide new theoretical basis of electroacupunture on the treatment of gastrointestinal motility disorders.

胃肠道ICC损伤或缺失是多种胃肠动力障碍性疾病的发病机制。目前已研究证实ICC损伤与胃肠道巨噬细胞聚集活化密切相关，我们前期研究发现电针足三里减少ICC损伤，修复ICC网状结构，从而改善胃肠动力。电针足三里能否通过调节胃肠道巨噬细胞聚集活化修复ICC，其机制有待进一步探讨。本项目拟在前期研究基础上，采用GFP骨髓移植等技术，研究电针刺激能否通过影响髓系分化减少胃肠道巨噬细胞的聚集，通过影响MCP-1/CCR2及下游MAPK通路调节单核细胞迁移，通过M-CSF/c-FMS及细胞内JAK/STAT3通路影响单核细胞分化；进一步探究电针刺激是否通过下调STAT1、NF-κB通路，上调JAK/STAT6通路调节巨噬细胞活化；更进一步探讨电针刺激调节巨噬细胞活化后对ICC作用机制，是否通过调节体内炎症因子水平，减少ICC凋亡和氧化应激损伤，为电针治疗胃肠动力障碍性疾病的临床应用提供新的理论依据。

胃肠道ICC损伤或缺失是多种胃肠动力障碍性疾病的发病机制。目前已研究证实ICC损伤与 胃肠道巨噬细胞聚集活化密切相关，我们前期研究发现电针足三里减少ICC损伤，修复ICC网状结构，从而改善胃肠动力。电针足三里能否通过调节胃肠道巨噬细胞聚集活化修复ICC，其机制有待进一步探讨。本项目在前期研究基础上，采用GFP骨髓移植等技术，证实电针刺激通过影响髓系分化减少胃肠道巨噬细胞的聚集，通过影响MCP-1/CCR2及下游MAPK通路调节单核细胞迁移，通过M-CSF/c-FMS及细胞内JAK/STAT3通路影响单核细胞分化;证实电针刺激调节巨噬细胞活化M1型和M2型活化;更进一步证实电针刺激调节巨噬细胞活化后对ICC作用机制，通过调节体内炎症因子水平，减少ICC凋亡和氧化应激损伤，为电针治疗胃肠动力障碍性疾病的临床应用提供新的理论依据。