前炎性单核/巨噬细胞活化在抑郁/焦虑恶化炎症性肠病中的相关机制探讨

研究表明抑郁/焦虑等负面情绪与炎症性肠病（IBD）关系密切，但其机制尚不清楚。 近年来心理神经免疫学研究示前炎性单核/巨噬细胞可能在抑郁/焦虑等心理精神疾病的发生发展中有重要作用。我们前期研究发现，伴有抑郁/焦虑的IBD患者症状更重，激素治疗效果更差；外周血M1型巨噬细胞生物标志物明显升高，且与抑郁评分呈正相关。因此我们推测抑郁诱导的前炎性单核/巨噬细胞活化，极可能是心理精神因素调节IBD炎症关键环节。本项目拟以伴有抑郁/焦虑症的IBD患者为研究对象，从体内外水平，观察伴抑郁/焦虑症的IBD患者前炎性单核/巨噬细胞的表型与功能，及其所诱导的低度全身性炎症反应和Th细胞分化，分析与此相关的肠道病理改变、肠道上皮细胞屏障和糖皮质激素抵抗机制，同时在动物模型上进一步证实这一假设。希望通过本研究初步阐释抑郁/焦虑等心理精神因素恶化IBD的免疫机制，为伴抑郁/焦虑症IBD特异靶向治疗提供新思路。

Lots of evidences have shown that depression/anxiety can aggravate the inflammation of Inflammatory Bowel Disease (IBD). However, the mechanism is not clear yet. Recently, neuroimmunological studies have confirmed that pro-inflammatory monocyte/macrophage plays a key role in the pathogenesis of psychosomatic disease including depression/anxiety. Our previous results have shown that IBD patients with depression/anxiety had more severe symptom and worse therapeutic effect of steroids than the IBD patients without depression/anxiety. At the same time, the level of M1 macrophage cytokines were higher and was positively related to the depression scores. Based on those data, we hypothesize that depression-driving activation of pro-inflammatory monocyte/macrophage may be one of the key factors in how depression/anxiety aggravates IBD. This project will focus on IBD patients with depression/anxiety only, and will use flow cytometry assay, qPCR, Luminex xMAP, immunofluorescence, etc, to investigate the function and phenotypes of pro-inflammatory monocyte/macrophage, the pro-inflammatory monocyte/macrophage-related low-grade systemic inflammation, T cell polarization, and to explore intestinal inflammation, intestinal epithelial barrier, glucocorticoid resistance. We will also confirm the hypnosis in animal studies. We wish to elucidate the immunological mechanism of depression/anxiety worsening IBD, and provide with scientific evidence for treatment of IBD patients with depression/anxiety.