基于Ezrin-ACAP4通路的调气活血养阴法调控胃酸分泌阻断慢性萎缩性胃炎“炎癌转化”的机制研究

慢性萎缩性胃炎（CAG）是慢性胃炎向胃癌转化的关键阶段，阻断慢性萎缩性胃炎“炎癌转化”是预防胃癌发生的有效途径。“调气活血养阴法”是国医大师路志正教授提出的CAG核心治法，临床疗效显著。在国家自然科学基金支持下，我们在整体动物水平证实了其能够有效阻断慢性萎缩性胃炎“炎癌转化”的作用，同时发现其能够调控胃酸分泌重要通路Ezrin-ACAP4相关蛋白，提高胃酸分泌水平，改善胃黏膜炎症状态，但其如何通过调控胃酸分泌达到阻断“炎癌转化”的具体机制尚不清晰。本项目将在前期研究基础上，以CAG胃酸分泌异常为切入点，应用“动物-类器官-细胞”多个模式体系，从动态的视角，探索“调气活血养阴法”代表方慢痞消调控胃酸分泌改变疾病进展的内在机制。研究成果将为寻找“炎癌转化”关键靶标以及临床应用中医药阻断慢性萎缩性胃炎“炎癌转化”提供有力证据，所建立的多维度研究模式也将为中西医结合药效学及药理学研究提供示范。

Chronic atrophic gastritis (CAG) is a key stage in the transformation from chronic gastritis to gastric cancer. “Regulating qi, activating blood and nourishing Yin” is the core therapeutic method of CAG proposed by professor Lu zhizheng, a master of traditional Chinese medicine. Under the support of national natural science foundation of China, we have proved it can effectively block the "inflammatory carcinoma transformation", and reduce the gastric cancer incidence in the animal experiment. In addition, it could regulate the Ezrin-ACAP4 pathway related proteins to increase the gastric acid secretion, improve stomach inflammation state, and finally control the CAG pathological progress. However, the specific mechanism of block "inflammatory carcinoma transformation" through regulating gastric acid secretion is unclear. This project will based on the previous research, taking abnormal gastric acid secretion as the entry point, applying multiple model systems of "animal-organoid-cell", observing the correlation between gastric acid secretion and pathological evolution in the process of "transformation of inflammatory carcinoma" to explore the key mechanism of acid secretion change affecting disease progression. The research results will provide strong evidence for finding the key target of "transformation of inflammatory cancer" and the clinical application of traditional Chinese medicine to block the "transformation of inflammatory cancer" of chronic atrophic gastritis. The established multiple model systems will also provide a demonstration for the pharmacodynamics and pharmacology of integrated traditional and western medicine.