苦味方剂香连丸经“苦味受体-肠巨噬细胞吞噬功能”路径治疗溃疡性结肠炎的分子机制研究

肠巨噬细胞强烈的吞噬能力是恢复溃疡性结肠炎（ulcerative colitis，UC）肠道稳态的关键，苦味受体作为一种新颖免疫受体在巨噬细胞上表达，激活后触发味觉级联信号，增强吞噬能力。前期研究结果表明：苦味方剂香连丸上调苦味觉信号中IP3R-1的表达，增强肠巨噬细胞吞噬能力，缓解UC肠道症状。因此，我们推测其效应机制可能与激活苦味受体触发味觉级联信号进而增强肠巨噬细胞吞噬能力有关。为此，拟建立UC小鼠模型和基因敲降细胞模型，采用real-time PCR、DARTS、分子对接等技术筛选与香连丸影响肠巨噬细胞吞噬能力高度相关的苦味受体亚型，再利用活细胞成像、流式细胞术等方法重点阐明基于“苦能燥湿”药性理论的“苦味方剂”香连丸通过调控“苦味受体-肠巨噬细胞吞噬能力”路径治疗UC的分子效应机制。

The strong phagocytic ability of intestinal macrophages is to restore the intestinal homeostasis of ulcerative colitis (UC). Bitter receptor, a novel immune receptor, is expressed on macrophages and activated to trigger taste signal pathway to enhance phagocytic ability. Previous studies showed that: bitter formula Xianglian pill up-regulated the expression of IP3R-1 in bitter taste signal, enhanced the phagocytosis of intestinal macrophages, and further alleviated the symptoms of UC. Therefore, we speculate that the mechanism of the Xianglian Pill may be related to activation of bitter receptors, triggering taste signal pathway，and enhancing phagocytosis of intestinal macrophages. Consequently, we are preparing to establish the UC mouse model and gene knockdown cell model, real-time PCR, DARTS, molecular docking，and other techniques to screen the subtypes of bitter receptors that are highly related to the effect of Xianglian Pill on phagocytosis of intestinal macrophages. Based on the theory of "bitter can dry dampness", through living cell imaging, flow cytometry，and other techniques, we are aiming to clarify the molecular mechanism of the "bitter formula" Xianglian pill regulating the "bitter receptor- intestinal macrophage phagocytosis" pathway in the treatment of UC.