中文摘要
感染后肠易激综合征(PI-IBS)是IBS常见类型,肠机械屏障损伤是导致PI-IBS腹泻的关键病理环节。传统名方痛泻要方为治疗该病最常用有效方剂。理论及拆方实验研究发现,“补散”药对白术/防风能协同止泻、改善肠屏障通透性,为痛泻要方起效的关键配伍,而其中白术可修复肠上皮细胞与紧密连接,防风能抗炎、抑制肠粘膜PAR-2、MLCK表达,故我们认为:白术/防风协同止泻是通过修复肠机械屏障、消除肠屏障损伤因子、调控肠屏障损伤关键信号通路,多靶点、多途径起效的。据此,本项目拟应用活体荧光成像、基因沉默等技术观察白术/防风对PI-IBS动物肠机械屏障功能和结构,肠屏障损伤因子及Caco-2细胞PAR-2 /CaM/MLCK信号通路的调控效应,阐明其重塑肠机械屏障的作用及其分子机制。旨在揭示白术/防风补散配伍的科学内涵,为中医药治疗本病的研究提供新靶点新思路,对阐释中药药性理论具有重要的学术意义。
英文摘要
Post infectious irritable bowel syndrome(PI-IBS) is the common type of IBS. Intestinal mechanical barrier injury is the key pathological point of PI-IBS diarrhea. Tong-xie-yao-fang prescription is the most commonly used and effective prescription for the treatment of PI-IBS. Theoretical and Experimental Researches have showed that couplet medicines of Rhizoma Atractylodis macrocephalae and Saposhnikovia divaricata which had the effect of restoring deficiency and dispersing evil could synergistically improve the diarrhea and intestinal barrier permeability. It is regarded as the key compatibility of medicines in Tong-xie-yao-fang prescription. Rhizoma Atractylodis macrocephalae can repair the intestinal epithelial cells and the tight juntction, while Saposhnikovia divaricata has the effect of anti-inflammatory and inhibiting the expression of intestinal mucosal PAR-2 and MLCK. Therefore, we assume that the effect of Rhizoma Atractylodis macrocephalae and Saposhnikovia divaricata is through repairing the intestinal mechanical barrier, eliminating the factors which make intestinal barrier damage and regulating the key signaling pathways of intestinal barrier dysfunction, which shows a synergistic effect of multiple targets and multiple ways .Accordingly, the effects of Rhizoma Atractylodis macrocephalae and Saposhnikovia divaricata on intestinal mechanical barrier function, structure and intestinal barrier damage factors in PI-IBS animals will be investigated by fluorescence imaging technique. Moreover, the effects of Rhizoma Atractylodis macrocephalae and Saposhnikovia divaricata on PAR-2 /CaM/MLCK signaling pathway in Caco-2 cell will be studyed by gene silencing technology . These will clarify the effect and molecular mechanism of Rhizoma Atractylodis macrocephalae and Saposhnikovia divaricata on remodeling intestinal mechanical barrier . This project will reveal the scientific connotation of restoring deficiency and dispersing evil and discover new target and new idea for the treatment of this disease in TCM. In addition, it has important academic significance on illustrating the theory of properties of chinese medicinal herbs.
