Akkermansia muciniphila调控MCP-1/CCR2轴改善肥胖胰腺炎重症化的作用机制研究

肥胖患者发生急性胰腺炎后病情重，感染率高，然而相关机制尚不明确。我们前期发现肥胖小鼠肠道A.muciniphila丰度降低，而给予其A.muciniphila灌胃后胰腺炎症状减轻。A.muciniphila作为一种新型益生菌在肥胖胰腺炎中的作用机制目前尚不清楚。肥胖小鼠发生胰腺炎时，血清趋化因子MCP-1浓度升高，同时胰腺巨噬细胞浸润增加，而给予A.muciniphila灌胃后上述表型被逆转，提示肥胖小鼠肠道A.muciniphila丰度降低可能通过调控MCP-1/CCR2轴介导胰腺巨噬细胞浸润，影响胰腺炎进展。本课题拟在前期基础上，深入探索A.muciniphila与肥胖胰腺炎患者严重程度的关系；并阐明其具体作用和相关分子机制。为肥胖胰腺炎患者的防治提供新靶点和理论支撑。

Obesity with pancreatitis are not only serious, but also have a high infection rate, but the related mechanism is not clear. Our previous studies found that the abundance of intestinal A. muciniphila in obese mice decreased, but the severity of pancreatitis were alleviated after oral supplementation with A. muciniphila in obese mice. The related molecular mechanism of A. muciniphila as a new type of probiotic in obese pancreatitis is currently unclear. When pancreatitis occurs in obese mice, the concentration of serum chemokine MCP-1 increases and the infiltration of pancreatic acinar macrophages increases. However, the phenotype was reversed after oral administration of A. muciniphila. It is suggested that the decreased abundance of A. muciniphila in obese mice may affect the progress of pancreatitis by regulating the infiltration of pancreatic macrophages mediated by MCP-1/CCR2 axis.The purpose of this study is to explore the relationship between A. muciniphila and the severity of obese AP patients on the basis of the previous period, and to clarify its specific role and related molecular mechanism. To provide a new target and theoretical support for the prevention and treatment of obesity with pancreatitis.