基于miR-34a介导Sirt1/mTOR通路研究艾灸抗CD肠纤维化机制

纤维化是克罗恩病（CD）常见而治疗最为棘手的难题。本课题组在以往大量针灸治疗CD及肠纤维化有效的基础上，以“肠成纤维细胞是导致CD肠纤维化的主要细胞”为切入点，运用现代分子生物学技术和方法，试图从体内动物实验和体外细胞实验相结合的方法研究：①拟证实CD肠道慢性炎症与损伤修复的主要介质Snail和α-SMA表达异常，自噬相关分子LC3-Ⅱ/LC3-Ⅰ和pBcl-2/Bcl-2的表达异常，miR-34a介导Sirt1/mTOR通路参与CD肠纤维化和CD结肠组织自噬活性的调节，miR-34a是克罗恩病肠纤维化的关键致纤维化因子之一；②初步阐释艾灸可能通过影响miR-34a的表达，作用SIRT1/mTOR通路，调节CD肠纤维化和结肠自噬活性，以达到提高针灸治疗克罗恩病肠纤维化的临床疗效之目的，为针灸治疗克罗恩病肠纤维化效应机制的阐明提供科学实验资料及理论基础。

Transmural fibrosis of Crohn's disease (CD) can erode the whole layers of the intestinal wall. Based on the promising effectiveness of moxibustion in the treatment of intestinal fibrosis of CD in the past, we consider that abnormal autophagy of fibroblasts may be the key mechanism of fibrosis, and try to study with in vivo animal experiment and in vitro cell experiment by using modern molecular biology techniques and methods, To confirm: ① The abnormal expression of the main medium of Snail and α-SMA in CD of chronic intestinal inflammation and injury repair, the abnormal expression of autophagy related molecule LC3- II /LC3- II and pBcl-2/Bcl-2. MiR-34a is one of the key factors to fibrosis of CD which induced the Sirt1/mTOR pathway to play a role in the CD frbrosis and regulation of autophagy activity.② Make a preliminary explanation that moxibustion may affect the expression of miR-34a by acting on the SIRT1 / mTOR pathway, thereby modulating CD intestinal fibrosis and colon autophagic activity, objective to improve the clinical efficacy of acupuncture and moxibustion in the treatment of Crohn's disease, to provide scientific experimental data and theoretical basis for the elucidation of the mechanism of acupuncture and moxibustion in the treatment of intestinal fibrosis in Crohn's disease.