清肠栓恢复肠道菌群治疗溃疡性结肠炎的作用及机制研究

Ulcerative Colitis (UC) is a medically refractory disease defined by World Health Organization, and its morbidity in China rises year by year. Traditional Chinese Medicine (T.C.M.) has incomparable advantage in UC treatment. Our team has been committed to treating UC and preventing its onset by T.C.M, over the past 30 years. We have developed an effective herbal suppository (Qingchang Suppository), as rectum colitis and sigmoid colits are the most common type of UC in Chinese people. Our previous studies have demonstrated that, Qingchang Suppository could achieve 91.49% clinical efficiency in mild to moderate UC; and there were multi-mechanisms behind its effect, such as reducing pro-inflammatory factors, restricting excessive immunce response, and regulating immune system. On the basis of these results, as well as the methods in modern molecular biology, we intend to explore the role of gut microbiota on UC and its relative mechanism, through gut microbiota transplantion induced colitis models; to explore whether Qingchang Suppository firstly restores intestinal homeostasis, then suppresses NF-κB activation and inflammatory mediators, and then treats UC, through an in vivo (Qingchang Suppository + UC gut microbiota transplantion) and in vitro (Qingchang Suppository treats Bifidobacterium and Lactic Acid Bacteria) study. In order to further provide experimental evidences for the extensive application of Qingchang Suppository in UC treatment.

溃疡性结肠炎(UC)被世界卫生组织列为难治性疾病，其在中国的发病率逐年上升。中医药治疗UC有显著疗效。本课题组过去30余年一直致力于中医药防治UC的研究，根据我国UC患者病变部位多在直-乙状结肠的特点，研发出纯中药有效栓剂-清肠栓。前期研究证明清肠栓治疗轻-中度UC的临床有效率高达91.49%，其具有下调炎症细胞因子，抑制过度的免疫应答，调节免疫平衡等作用。本课题拟在前期研究基础上，采用现代生物学方法和技术，以肠道菌群移植制备UC大鼠模型，探究肠道菌群在UC发病中的作用及作用机制；通过清肠栓制备的UC粪菌液灌肠的体内研究，以及清肠栓直接干预乳酸菌和双歧杆菌的体外研究，明确清肠栓是否通过恢复肠道微生态平衡，抑制NF-κB信号通路，调节免疫应答从而治疗UC。为清肠栓治疗UC的应用和推广提供实验依据。

溃疡性结肠炎(UC)被世界卫生组织列为难治性疾病，其在中国的发病率逐年上升。中医药治疗UC有显著疗效。本课题组过去30余年一直致力于中医药防治UC的研究，根据我国UC患者病变部位多在直-乙状结肠的特点，研发出纯中药有效栓剂-清肠栓。前期研究证明清肠栓治疗轻-中度UC的临床有效率高达91.49%，其具有下调炎症细胞因子，抑制过度的免疫应答，调节免疫平衡等作用。本课题在前期研究基础上，以肠道菌群移植制备UC大鼠模型，发现肠道菌群在UC发病中的起着协同致病作用，其作用机制与进一步激活TLR4/MYD88/NF-κB通路，抑制脾脏/肠系膜淋巴结CD4+CD25+Foxp3+Treg细胞，以及促进结肠炎症细胞因子IL-12/IL-23/IL-6/TNF-a释放有关。通过清肠栓制备的UC粪菌液灌肠的体内研究，以及清肠栓直接干预两歧双歧杆菌和多形拟杆菌的体外研究，证实清肠栓对于肠道菌群紊乱有恢复作用，其机制与抑制TLR4/MYD88/NF-κB通路，上调脾脏/肠系膜淋巴结CD4+CD25+Foxp3+Treg细胞，以及减少炎症细胞因子IL-12/IL-23/IL-6/TNF-a释放有关。