Parasutterella excrementihominis通过调控巨噬细胞M1/M2极化诱导肠易激综合征发生发展的机制研究

Irritable bowel syndrome (Irritable Bowel Syndrome, IBS) is a chronic disease which seriously affects the life and work of patients. At present, it is believed that intestinal flora plays an important role in the pathogenesis of IBS, but its mechanism needs to be further explored. Our previous study showed that the expression of Parasutterella excrementihominis in the intestinal flora of IBS patients was significantly increased and positively correlated with macrophage infiltration.It has been proved that the this kind of bacteria can secrete propionic acid and promote the secretion of IFN- γ from intestinal epithelium.In our research, it was found that the expression of IFN- γ was increased in intestinal tissue of IBS mice, which active the JAK/STAT1 pathway, and the expression of IL-12 and NOS2, the inflammatory cytokines of M1 macrophage marker, was also increased significantly. In this study, we use the cell experiments and animal experiments to studied that Parasutterella excrementihominis promoted the release of IFN- γ from intestinal epithelial cells by propionic acid, further activated the JAK/STAT1 pathway and regulated the M1/M2 polarization of macrophages, thus promote the progression of IBS.

肠易激综合征（IBS）是一种严重影响病人生活和工作的慢性疾病，目前研究认为肠道菌群在IBS的发病过程中起十分重要的作用，但其作用机制有待进一步探究。我们前期研究发现IBS患者肠道菌群中Parasutterella excrementihominis表达丰度显著提高，并和巨噬细胞浸润呈显著正相关。已有研究证实该菌可分泌丙酸促进肠上皮分泌IFN-γ，而本课题组移植肠道菌群构建IBS小鼠模型，其肠道中IFN-γ表达升高，JAK/STAT1通路激活，且M1型巨噬细胞标志的炎性因子IL-12和NOS2的表达也显著升高。因而本研究结合前期工作，通过细胞实验和动物实验，研究Parasutterella excrementihominis通过代谢产物丙酸促进肠上皮细胞释放IFN-γ，进一步激活JAK/STAT1通路从而调控巨噬细胞M1/M2极化，进而诱导IBS进展的具体分子机制。

肠易激综合征（Irritable Bowel Syndrome, IBS）是慢性疾病，有时会引起肠道失能，严重影响病人的生活和工作。本研究对肠易激综合征相关的差异表达基因和肠易激综合征有关的药物及其靶向基因进行了分析，获得了35个肠易激综合征关键基因，同时这35个肠易激综合征关键基因富集在了29个通路，可能与尼古丁成瘾、谷氨酸受体活性密切相关，并可影响T cells CD4 memory resting、Eosinophils两种免疫细胞的浸润。通过mRNA-miRNA、mRNA-TF、TF-miRNA的网络分析，我们发现基因VEGFA均处于关键位置。进一步在成功构建的IBS小鼠模型中行免疫组化再次验证了VEGFA在IBS小鼠中异常表达，因此VEGFA很可能是肠易激综合征的潜在治疗靶点。

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