基于Ezrin-ACAP4信号通路的调气活血养阴法治疗大鼠慢性萎缩性胃炎的作用机制研究

Chronic atrophic gastritis (CAG) is the key stage in the transformation from chronic gastritis to gastric cancer, of which the occurrence and development are closely related to the abnormal secretion of gastric acid. The therapy of supplementing and regulating qi, activating blood and nourishing yin is the core treatment of CAG proposed by the master of traditional Chinese medicine, Professor Lu Zhizheng, which has a good clinical effect. There are much important clinical and scientific research value for analyzing its mechanism. In recent 5 years, our previous studies showed that the Ezrin-ACAP4 signal pathway is directly related to the secretion function of gastric acid. At the same time, we also did the related studies between Traditional Chinese medicine drug combination of supplementing and regulating qi, activating blood and nourishing yin therapy and secretion function of gastric acid. Based on the previous research, this project intends to observe the key factors of CAG gastric acid secretion abnormality and the effect of CAG on gastric acid secretion in CAG rats from the whole animal level was systematically studied. A variety of molecular biology techniques were used to analyze the changes of Ezrin-ACAP4 signal pathway-related proteins and gastric acid secretion-related serological markers in gastric mucosa, and the gastric acid secretion function was controlled by the method of supplementing and regulating qi, activating blood and nourishing yin, the mechanism of control of disease progression. In order to reveal the scientific connotation of Professor Lu Zhizheng's core treatment of CAG. It is very helpful to guide the clinical application and transformation of famous doctors' experience.

慢性萎缩性胃炎（CAG）是慢性胃炎向胃癌转变的关键阶段，其发生、发展与胃酸分泌异常密切相关。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，疗效显著，解析其作用机制具有重要的临床和科研价值。我们近5年的工作揭示了Ezrin-ACAP4通路与胃酸分泌的相关关系，同时初步开展了调气活血养阴法部分药物调节CAG大鼠胃酸分泌功能的相关研究。本项目在前期研究基础上，立足CAG胃酸分泌异常这一关键因素，拟从整体动物水平，采用路老调气活血养阴法代表方剂慢痞消，系统观察其对CAG大鼠胃酸分泌的影响，同时应用多种分子生物学技术手段，检测大鼠胃黏膜Ezrin-ACAP4通路相关蛋白及胃酸分泌相关血清学指标的变化情况，以解析调气活血养阴法通过该通路调控胃酸分泌功能以治疗大鼠CAG、控制疾病进展的作用机制，为揭示路老治疗CAG核心治法的科学内涵、指导名医经验临床应用和转化起到积极的推动作用。

慢性萎缩性胃炎（CAG）是慢性胃炎向胃癌转变的关键阶段，其发生、发展与胃酸分泌异常密切相关。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，疗效显著，解析其作用机制具有重要的临床和科研价值。本项目优化并建立了大鼠CAG病证结合动物模型；观察了调气活血养阴法代表方慢痞消对CAG大鼠胃黏膜组织形态及胃壁细胞超微结构的改变情况，评价了其对CAG的治疗作用；分析了慢痞消对CAG大鼠胃酸分泌的影响以及对Ezrin-ACAP4通路相关蛋白表达水平的变化情况，探讨了其通过Ezrin-ACAP4通路调控胃酸分泌功能的内在机制。研究显示，路老治疗CAG的经验方“慢痞消”能够有效改善大鼠病理状态，并通过调控Ezrin-ACAP4信号通路达到控制病理进展的作用。该项目的开展，为揭示路老治疗CAG核心治法的科学内涵、指导名医经验临床应用和转化起到推动作用。