治疗胃癌前病变（GPL）对阻断炎癌转化至关重要。健脾化瘀解毒方治疗GPL疗效确切，但机制尚未阐明。程序性细胞坏死与GPL炎癌转化密切相关，且高浓度ROS引起线粒体损伤、诱导p62过度合成及PARP-1过度释放是导致程序性细胞坏死的关键连续事件。我们发现，GPL存在局部低氧，线粒体损伤，坏死相关基因p62和RIP1异常高表达，健脾化瘀解毒方可调控p62和RIP1表达，改善缺氧状态。由此，提出“健脾化瘀解毒方以ROS-p62-PARP-1通路调控程序性细胞坏死修复受损线粒体，阻断炎癌转化治疗GPL”的假说。为此，在前期基础上，利用Hp感染Atp4a-/-小鼠复制GPL，并采用p62-/-小鼠、PARP-1沉默/过表达细胞从正向及负向两个方面，整体-细胞-分子三个水平评价ROS-p62-PARP-1介导程序性细胞坏死调控GPL炎癌转化过程及健脾化瘀解毒方的干预作用，为中药复方临床应用提供依据。

Effective treatment of gastric precancerous lesion (GPL) is essential to block the transformation from gastritis to malignancy. The clinical efficacy of Jianpi Huayu Jiedu Formula in the treatment of GPL is confirmed, but the mechanism has not been well clarified. Studies have confirmed that necroptosis is closely related to the inflammation-cancer transformation of GPL, and the increased ROS causes mitochondrial damage, which induces p62 synthesis and PARP-1 release. If this pathway is overly stimulated, the over-synthesized p62 and over-released PARP-1 results in necroptosis directly. Our previous studies have found that local hypoxic microenvironment presents in GPL. Mitochondrial damage and abnormally high expression of necrosis-related genes p62 and RIP1 exists in the gastric mucosa during the GPL stage. We have revealed that Jianpi Huayu Jiedu Formula could regulate the expression of p62 and RIP1 and improve the hypoxic state of GPL as well. Therefore, we propose that "Jianpi Huayu Jiedu Formula plays an important role in regulating the ROS-p62-PARP-1 signal pathway, and achieves the purpose of inhibiting necroptosis of gastric epithelial cells, then repairs damaged mitochondria and blocks the transformation from gastritis to malignancy". In order to prove the hypothesis, we will establish the GPL animal model with Atp4a-/-mice infected by Helicobacter Pylori based on our previous studies. At the same time, the p62-/-mice, PARP-1 silenced and highly expressed cells will be applied to the project. We will perform our study from the forward and reverse aspects and on the three levels of whole-cell-molecule, and aim to reveal the key role of the necroptosis mediated by the ROS-p62-PARP-1 signal pathway in the inflammation-cancer transformation in GPL and clarify the intervening effect of Jianpi Huayu Jiedu Formula. More importantly, we hope this study can provide scientific evidence for the clinical application of traditional Chinese medicine compounds.