健脾运中祛毒方调控NF-κB通路介导的“自噬-线粒体稳态-炎症反应”途径逆转胃癌前病变的机制研究

胃癌前病变(Gastric precancerous lesions, GPL)是发展为胃癌的关键病理阶段，探寻GPL的防治策略是切断胃癌进展路线并降低其发生率的最佳途径。本项目基于GPL“脾虚为本，久病致瘀”的病机特点，以“虚”“瘀”“毒”作为论治GPL的关键三要素，从健脾运中祛毒立论临证疗效颇佳。目前，明确中药复方的作用靶点一直是中医药现代化研究的重点。我们体内实验研究表明，健脾运中祛毒方可抑制胃黏膜炎症并一定程度逆转GPL病理改变；同时结合高通量测序、WB及透射电镜等结果，已明确NF-κB通路、自噬及线粒体功能障碍参与了GPL“炎-癌”转变的病理进展。因此，本项目拟在前期研究基础上，将“自噬-线粒体稳态-炎症反应”的前言病理机制与“胃癌前病变动态可逆转”的临床问题相对应，探讨健脾运中祛毒方的效应机制并明确GPL的发展与转归。

Gastric precancerous lesions (GPL) is a key pathological stage in the development of gastric cancer. Exploring GPL prevention strategies is the best way to cut the progression of gastric cancer and reduce its incidence. The project is based on the pathogenesis characteristics of“spleen deficiency-based, chronic disease-induced stasis”, and uses "deficiency", "stasis", "poison" as the three key elements to treat GPL. Based on the theory of strengthening the spleen and removing blood stasis and detoxification, the clinical effect is quite good. At present, clarifying the target of the traditional Chinese medicine compound has always been the focus of modernization of traditional Chinese medicine. Our experiments showed that Jianpi Yunzhong Qudu decoction can inhibit gastric mucosal inflammation and reverse the pathological changes of GPL to a certain extentin in vivo. At the same time, combined with the results of high-throughput sequencing, Western blotting, and transmission electron microscopy, we had been clarified that the NF-κB signaling pathway, autophagy, and mitochondrial dysfunction were involved in the pathological progress of GPL "inflammatory-cancer" transition. Therefore, on the basis of previous research, the project intends to correspond the pathological mechanism of "autophagy-mitochondrial function- inflammatory response" homeostasis with the clinical problem of "dynamic reversibility of gastric precancerous lesions" for the first time, and explore the effects mechanism of JPYZQD, then clarified the development and outcome of the GPL.