基于肠黏膜屏障改变探究白术泔制增强健脾止泻效应的物质基础及作用机制

白术为临床常用大宗品种，生白术和泔制白术治疗溃疡性结肠炎（UC）已为临床验证，课题前期已明确其泔制工艺具有科学合理性，炮制后体外化学成分变化明显，具有补脾作用。基于此，本课题采用LC-MS/MS指纹轮廓谱和MALDI-MS质谱成像分析方法，全面动态表征白术炮制前后体内化学成分变化规律，识别白术、泔制白术的关键入体活性成分。通过DSS诱导复制UC小鼠模型，动态观察正常及疾病状态下UC的肠黏膜屏障结构、功能、损伤机制，运用代谢组学、蛋白质组学、质谱成像、16S rRNA基因测序、Western-Blot分析等手段，探讨白术和泔制白术药效作用，阐明泔制白术通过调节机械屏障claudin-2蛋白、化学屏障黏蛋白MUC、免疫屏障免疫球蛋白SIgA表达及改善生物屏障菌群，同时调控相关信号通路，综合阐释白术泔制增强健脾止泻效应的物质基础及作用机制，为指导临床治疗提供理论依据。

Atractylodis Macrocephalae is a common clinical variety.The treatment of ulcerative colitis ( UC ) by raw Atractylodes macrocephala Koidz and swill Atractylodes macrocephala Koidz has been clinically verified. The swill processing technology has been confirmed to be scientific and reasonable in the early stage of the subject. The chemical composition changes in vitro after processing are obvious, and it has the effect of tonifying the spleen. Based on this, LC-MS / MS fingerprint profile and MALDI-MS mass spectrometry imaging analysis method were used to comprehensively and dynamically characterize the changes of chemical components in Atractylodes macrocephala before and after processing, and identify the key active ingredients of Atractylodes macrocephala and Atractylodes macrocephala swill. The UC mouse model was induced by DSS to dynamically observe the intestinal mucosal barrier structure, function and damage mechanism of UC under normal and disease conditions. Metabonomics, proteomics, mass spectrometry imaging, 16S rRNA gene sequencing, and Western Blot analysis were used to explore the efficacy of Atractylodes macrocephala Koidz and Atractylodes macrocephala Koidz made from swill. It was clarified that Atractylodes macrocephala Koidz made from swill could regulate the expression of claudin-2 protein,MUC, and SIgA to improve the biological barrier flora, and regulate related signaling pathways, comprehensively explain the material basis and mechanism enhancing the effect of invigorating spleen and relieving diarrhea, and provide a theoretical basis for guiding clinical treatment.