益气养阴活血解毒法调节"产乳酸菌-短链脂肪酸-NF-κB/NLRP3炎症小体"轴治疗胃癌前病变的机制研究

胃癌前病变（PLGC）是消化系统临床常见病、多发病，且PLGC是胃癌发生的关键阶段。益气养阴活血解毒法临床治疗PLGC效果显著，能从根本上逆转患者和PLGC模型大鼠胃黏膜病理损害。PLGC的发生发展及治疗与肠道菌群和慢性炎症密切相关，有效治疗PLGC是降低胃癌发生率的有效途径，前期研究证实产乳酸菌是PLGC的关键细菌，益气养阴活血解毒法可明显提升产乳酸菌丰度，延缓PLGC进展。短链脂肪酸是其主要代谢产物，NF-κB/NLRP3炎症小体是慢性炎症的关键通路且与短链脂肪酸密切相关。本项目在前期工作基础上，拟以产乳酸菌-短链脂肪酸-NF-κB/NLRP3炎症小体轴为切入点，结合菌群基因组学和代谢组学等方法，探究益气养阴活血解毒法对PLGC菌群组成及代谢产物和NF-κB/NLRP3的影响，阐明其作用机制，为临床应用以调节菌群平衡和控制炎症为靶标的中医药治疗PLGC提供科学依据。

Precancerous lesions of the stomach (PLGC) is a common and frequently-occurring disease of the digestive system, and PLGC is a key stage of the occurrence of gastric cancer. The method of replenishing qi, nourishing yin, activating blood and detoxifying has a significant clinical effect on PLGC, which can fundamentally reverse the pathological damage of gastric mucosa in patients and PLGC model rats. The occurrence, development and treatment of PLGC are closely related to the gut microbiota and chronic inflammation. Treatment of PLGC is an effective way to reduce the incidence of gastric cancer. Preliminary studies have confirmed that lactic acid bacteria (LAB) is the key bacteria of PLGC. The method of replenishing qi, nourishing yin, activating blood and detoxifying can significantly increase the abundance of LAB and delay the progress of PLGC. Short-chain fatty acids (SCFAs) are LAB’s main metabolites, and NF-κB/NLRP3 inflammasome is the key pathway of chronic inflammation and is closely related to SCFAs. Based on the previous work, this project intends to use the LAB-SCFAs-NF-κB/NLRP3 inflammatory corpuscle axis as the entry point, combining the methods of microbiota genomics and metabolomics to explore the effects of the method of replenishing qi, nourishing yin, activating blood and detoxification on PLGC microbiota and its metabolites and NF-κB/NLRP3, clarify its therapeutic mechanism and provide a scientific basis for the clinical application of TCM treatment of PLGC with the regulation of microbiota controlling inflammation as the target.