基于PKA/NLRP3炎症小体活化导致GES-1细胞焦亡探讨消化性溃疡“毒热”病因病机演变及“以痈论治”作用机制

国医大师周学文提出“毒热”为消化性溃疡主要病因，“以痈论治”获得良效，溃得康颗粒获批国家中药新药上市。但“毒热”病理基础、“以痈论治”作用机制有待深入研究。在前期研究基础上，本项目提出科学假说：消化性溃疡“毒热”病因病机演变的病理基础，与PKA/NLRP3炎症小体活化导致GES-1细胞焦亡密切相关；“以痈论治”代表方溃得康颗粒及其拆方在不同病机阶段发挥作用，其机制可能通过调控上述病理过程而获效。研究分为三部分：以临床消化性溃疡活动期胃毒热证患者、胃溃疡大鼠模型、Hp诱导GES-1细胞为研究对象，从PKA/NLRP3炎症小体活化导致GES-1细胞焦亡作为切入点，以溃得康颗粒及其拆方“清热解毒”“健脾和胃”“托腐生肌”针对不同病机阶段，探讨消化性溃疡“毒热”病因病机的病理基础，以及“以痈论治”作用靶点。本项目将为“毒热”病机研究提供新途径，为“以痈论治”消化性溃疡提供新证据。

Chinese medicine master Zhou Xuewen proposed that "toxic fever" is the main cause of peptic ulcer. "Treatment based on carbuncle" has achieved good results, and Kuidekang Granule has been approved as a new Chinese medicine. However, the pathological basis of "toxic fever" and the mechanism of "treatment with carbuncle" need further study. Based on the previous research, this project proposed a scientific hypothesis: the pathological basis of the evolution of the pathogenic pathogenesis of peptic ulcer "toxic fever" is closely related to the activation of PKA/NLRP3 inflammatory corpuscles leading to pyrolysis of GES-1 cells; "Fangkuidekang Granule and its disintegration play a role in different pathogenesis stages, and its mechanism may be effective by regulating the above pathological process. The study is divided into three parts: the patients with gastric poisoning and heat syndrome in the active stage of clinical peptic ulcer, rat model of gastric ulcer, and Hp-induced GES-1 cells are the research objects, and the activation of PKA/NLRP3 inflammatory bodies leads to the pyrolysis of GES-1 cells As an entry point, to explore the pathological basis of the pathogenesis of peptic ulcer "toxin fever" with Kuidekang granules and its disintegrations "clearing heat and detoxifying", "spleen and stomach", and "supporting rot and muscular muscles" The target of "Treatment with carbuncle". This project will provide a new way for the research on the pathogenesis of "toxic fever" and provide new evidence for the treatment of peptic ulcer by "carbuncle.