miR-146a调控溃疡性结肠炎大鼠肠道微生态变化及安肠汤干预机制研究

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, because the disease incidence increased year by year, the pathogenesis is not fully understood, and the lack of effective treatment, so explore the pathogenesis and find the effective drug intervention and treatment has been a research hotspots. miR-146a is now known more in-depth study of a miRNA and closely related with inflammation, have considerable contact with UC, but the causal relationship between the target and the key factors remains unclear, gut microflora imbalance is an important factor currently known closely associated with UC, intestinal microflora imbalance caused by miR-146a effects on the body's inflammatory and immune may be the mechanism of UC, and via miR-146a effects on the intestinal microflora regulation to explore the pathogenesis of UC, at home and abroad have not been reported. Anchang decoction is more than 20 years of clinical application and research of traditional Chinese medicine treatment of UC, has been shown with good clinical effect. This topic through the establishment of UC rat models to microRNA regulation of intestinal microflora change as the starting point, then explore the pathogenesis of UC, observe the intervention of anchang decoction on UC intestinal microflora and reveal its treatment of UC targets.

溃疡性结肠炎(UC)是一种慢性炎症性肠病，由于该病发病率逐年增加，发病机制尚未完全阐明，又缺乏有效的治疗药物，故探究其发病机制及寻找有效防治药物一直是研究热点。miR-146a是目前已知研究较为深入的与炎症反应密切相关的一种miRNA，与UC的有着相当的联系，但两者之间的因果关系及关键因素靶点仍不明确，肠道微生态失调是目前已知的与UC有着密切关联的重要因素，miR-146a通过对机体炎症免疫的影响而调控肠道微生态失调，可能是UC的发生机制，而以miR-146a对肠道微生态的调控来探索UC的发病机理，目前国内外尚未见有相关报道。安肠汤是课题组临床应用和研究20余年治疗UC的中药复方，临床疗效佳。本课题通过建立 UC 大鼠模型，以microRNA对肠道微生态变化的调控为切入点，进而探索UC发病机制，观察安肠汤对UC大鼠肠道微生态的干预作用，揭示其防治UC的作用靶点。

溃疡性结肠炎(UC)发病机制尚未完全阐明，又缺乏有效的治疗药物，故探究其发病机制及寻找有效防治药物一直是研究热点。我们研究建立UC大鼠模型，发现与正常组比较，模型组大鼠miRNA-146a表达水平显著降低，炎症相关因子IL-17、IL-10水平升高，IL-10含量降低，UC大鼠经予安肠汤灌胃后，大鼠miRNA-146a表达水平增高，IL-17、IL-10表达水平显著降低，且与安肠汤的给药浓度有关。而大鼠肠道微生态中，UC大鼠粪便与空白组比较益生菌双歧杆菌属、乳杆菌属含量变高含量较低，致病菌大肠杆菌属、志贺菌属、拟杆菌属含量较高，肠道乙酸升高，血清内毒素含量较高。经安肠汤灌胃后，大鼠粪便中双歧杆菌属、乳杆菌属含量变高，大肠杆菌属、志贺菌属拟杆菌属含量降低，大鼠肠道乙酸、血清中内毒素含量降低，可见安肠汤可通过miRNA-146a、IL-17、IL-10、影响肠道微生态干预UC病情的发展，中医药治疗UC前景大，值得进一步推广。