胃癌前病变（GPL）是“慢性萎缩性胃炎→胃癌前病变→胃癌”炎-癌转化过程的关键阶段，治疗GPL对防治胃癌至关重要。前期研究发现，胃黏膜炎性反应可加快GPL恶性进展，Atp4a-/-胃癌前病变小鼠胃黏膜组织细胞焦亡相关蛋白GSDMD、Caspase-1表达异常，而健脾化瘀解毒方及有效成分可显著抑制胃黏膜炎症反应和细胞焦亡相关蛋白表达，且可选择性调控PKA。因此，本课题提出健脾化瘀解毒方通过PKA调控NLRP3炎症小体异常活化，抑制巨噬细胞焦亡，减少细胞因子释放，改善组织损伤、促进其修复以治疗GPL的假说。为此，拟通过构建PKA沉默和NLRP3高表达巨噬细胞，并利用Atp4a-/-胃癌前病变小鼠模型，检测该方对PKA活性及NLRP3炎症小体活化所介导的巨噬细胞焦亡的调控。从整体-细胞-分子层面探究巨噬细胞焦亡在GPL发展中的角色并为健脾化瘀解毒方防治GPL的临床应用提供科学依据。

Gastric precancerous lesions (GPL) are the key stage of the transformation process from chronic atrophic gastritis to precancerous lesions to gastric cancer.The treatment of GPL is very important for the prevention and treatment of gastric cancer.Previous studies have found that gastric mucosal inflammatory response can accelerate the malignant progression of GPL,and the expression of GSDMD and Caspase-1 in gastric mucosal cells of Atp4a-/-mice were abnormal.Jianpi Huayu Jiedu Formula and its active ingredients could significantly inhibit gastric mucosal inflammation and the expression of pyrogen-related protein,as well as selectively regulate the PKA gene.Therefore, this project proposes the hypothesis that Jianpi Huayu Jiedu Formula can regulate the abnormal activation of NLRP3 inflammasome through PKA, inhibit the macrophage pyroptosis,reduce the release of cytokines, improve tissue damage and promote its repair to treat GPL.To this end, we intend to construct the PKA silencing and NLRP3 overexpression macrophages,and use the GPL mouse model of Atp4a-/- duplicated in previous studies to detect the regulation of the prescription on PKA activity and NLRP3 inflammasome activation mediated macrophage pyroptosis.To explore the role of macrophage pyroptosis in the development of GPL from the whole-cell-molecule level and to provide scientific basis for the clinical application of Jianpi Huayu Jiedu recipe in the prevention and treatment of GPL.