逆流挽舟法调控tuft细胞促肠干细胞增殖修复溃疡性结肠炎黏膜的机制研究

修复损伤肠黏膜是治疗溃疡性结肠炎（ulcerative colitis，UC）的有效策略之一。肠干细胞是修复损伤肠黏膜的核心细胞，最新研究发现肠tuft细胞生成的IL-25可诱导干细胞增殖分化，并且其异常表达与UC有关。临床证实逆流挽舟法的代表方人参败毒散治疗UC有效，课题组前期研究发现该方对肠炎黏膜有修复作用。那么人参败毒散能否调节结肠局部免疫，影响与肠黏膜修复密切相关的干细胞，以实现肠屏障功能的维持？由此提出假说：人参败毒散可能通过tuft细胞分泌IL-25调控肠道局部免疫，促进干细胞增殖分化以修复UC损伤的肠黏膜。本项目拟以葡聚糖硫酸钠复制UC模型，采用IL-25基因敲除鼠，运用现代分子生物学检测技术，研究人参败毒散修复UC肠黏膜的调控途径和作用机制，为逆流挽舟法提供实证依据。这一研究对丰富中医治疗UC的治则治法，有重要的理论价值和临床应用前景。

Repairing injured intestinal mucosa is one of the effective strategies for the treatment of ulcerative colitis. Intestinal stem cells are the core cells to repair injured intestinal mucosa. Recent studies have found that IL-25 produced by intestinal tuft cells can induce stem cell proliferation and differentiation, and its abnormal expression is related to UC. It is proved that the representative prescription of hauling the boat upstream method, namely ginseng toxin-vanquishing powder, is effective in the treatment of UC. Our previous researches show that this prescription has a repairing effect on enteritis mucosa. So can ginseng toxin-vanquishing powder regulate the local immunity of colon and affect the stem cells closely related to the repair of intestinal mucosa, so as to maintain the intestinal barrier function? Therefore, it is hypothesized that ginseng toxin-vanquishing powder may regulate intestinal local immunity by secreting IL-25 from tuft cells and promote stem cell proliferation and differentiation to repair intestinal mucosa damaged by UC. In this project, we intend to duplicate UC model by dextran sulphate sodium (DSS), adopt IL-25 gene knock-out mice, and immunofluorescence, Western Blot and qRT-PCR detection techniques were used to study the regulatory pathway and mechanism of ginseng toxin-vanquishing powder in repairing UC intestinal mucosa, so as to provide empirical basis for hauling the boat upstream method. This study has important theoretical value and clinical application prospect for enriching the treatment principles and methods of traditional Chinese medicine in the treatment of UC.