基于MEK-ERK信号通路探讨温肾健脾调枢法对IBS-D大鼠作用机制的研究

Diarrhea-predominant irritable bowel syndrome (IBS-D) is the most common functional gastrointestinal disease. The incidence of IBS-D is up to 20%, and it is increasing year by year. The exploration of its formation mechanism and treatment methods is still the focus and difficulty in theory and practice. At present, western medicine treatment lacks effective means, and traditional Chinese medicine treatment has obvious advantages. Previous experiments showed that the method of warming the kidney, strengthening the spleen and regulating the pivot had good curative effect and low recurrence rate in the treatment of IBS-D. Previous studies have found that MEK-ERK signaling pathway may be related to the formation of IBS-D visceral hypersensitivity. Basic studies have found that traditional Chinese medicines such as warming the kidney, invigorating the spleen and regulating the pivot have effects on the upstream regulatory substances TNF-alpha, IL-1bet and downstream effector c-Fos of MEK-ERK signaling pathway. Based on the above considerations, this study focused on the upstream regulatory substances TNF-alpha, TNF-alpha receptor, IL-1bet and IL-1bet. The body and downstream effector c-Fos were studied to clarify the therapeutic effect of warming the kidney and invigorating the spleen and regulating the pivot on IBS-D, and to explore the mechanism of warming the kidney and invigorating the spleen and regulating the pivot on IBS-D. The implementation of the study will accumulate new ideas for further understanding the mechanism of TCM treatment of IBS, and better apply the results to clinical translational medicine and interdisciplinary.

腹泻型肠易激综合征（IBS-D）是最常见的功能性胃肠病，发病率高达20%，且呈逐年上升趋势，其形成机制和治疗手段探索仍是理论和实践的焦点与难点。目前西医治疗缺乏有效手段，中医药治疗优势显著。前期实验表明温肾健脾调枢法对IBS-D疗效好、复发率低。以往研究发现MEK-ERK信号通路可能与IBS-D内脏高敏性形成有关，相关基础研究发现温肾健脾调枢法等中药能够影响MEK-ERK信号通路上游调控物质TNF-α、IL-1β，下游效应物质c-Fos，基于以上考虑本研究围绕MEK-ERK信号通路及其上游调控物质TNF-α、TNF-α受体、IL-1β、IL-1β受体、下游效应物质c-Fos展开研究，阐明温肾健脾调枢法对IBS-D的疗效，深入探讨温肾健脾调枢法干预IBS-D的效应机制。研究的实施将为深入理解中医药治疗IBS的机制积累新思路，并将所获成果更好地应用于临床转化医学以及多学科交叉。

腹泻型肠易激综合征 (IBS-D) 是以反复发作的腹痛，或伴有排便习惯、粪便性状改变为主要临床表现的一类“肠-脑互动”异常性疾病，严重影响患者生活质量和工作效率，其形成机制和治疗手段探索仍是理论和实践的焦点与难点。目前西医治疗缺乏有效手段，中医药治疗具有一定特色。基于中医整体观及辨证论治思维，考虑脾肾阳虚为本病反复发作、迁延难愈的关键病机，并立温肾健脾调枢法，拟定温肾健脾调枢方，前期临床研究表明本方对IBS-D患者疗效由于安慰剂对照组、且能降低6个月的复发率。以往研究发现MEK-ERK信号通路可能与IBS-D内脏高敏感形成有关，相关基础研究发现温肾健脾调枢法等中药能够影响MEK-ERK信号通路上游调控物质TNF-a、IL-lβ，下游效应物质c-Fos，基于以上考虑本研究围绕MEK-ERK信号通路及其上游调控物质TNF-a 、TNF- 受体、IL-1B 、IL-1B受体、下游效应物质c-Fos展开，探究温肾健脾调枢法干预IBS-D的疗效及效应机制。项目成果将为深入理解中医药治疗IBS的机制积累新思路，应用于药物开发、临床转化以，并为多学科交叉提供研究基础。