益气化瘀解毒方通过调控JAK-STAT信号通路介导的EMT阻断慢性萎缩性胃炎“炎-癌”转化的作用机制研究

慢性萎缩性胃炎（CAG）是最常见的胃癌前疾病，绝大多数肠型胃癌由该病发展而来，治疗CAG是阻断胃炎向胃癌进展的重要环节。目前CAG的发病机制不明，西医治疗效果不佳。课题组前期研究发现中药复方益气化瘀解毒方在临床治疗CAG有效，进一步研究显示CAG存在JAK-STAT信号通路和EMT相关基因改变，益气化瘀解毒法对该途径基因和蛋白有改变。据此我们假设JAK-STAT信号通路介导的EMT异常在CAG发病中起重要作用，益气化瘀解毒方通过该途径发挥阻断CAG“炎-癌”转化的作用。为证实假设，拟在动物和细胞层面，结合抑制、过表达等技术，探讨该途径在CAG发病和益气化瘀解毒方干预的机制，并进一步通过网络药理学、分子对接和PEAQ-ITC等技术筛选出复方中调控该途径的有效成分，更深入探讨作用机制。为益气化瘀解毒方治疗CAG提供现代科学依据，为中医药延缓、逆转和预防胃癌前病变的中药新药研发提供思路和基础。

Chronic atrophic gastritis (CAG) is the most common pre-cancerous disease of the stomach, and most intestinal gastric cancers develop from this disease. At present, the pathogenesis of CAG is unknown and the effect of western medicine is unsatisfactory. Previous study by our research group show that the Traditional Chinese Medicine (TCM) prescription Yiqi Huayu Jiedu decoction is effective in the clinical treatment of CAG. Further studies revealed that CAG has JAK-STAT signaling pathway and EMT-related gene changes, and that the TCM method of Yiqi Huayu Jiedu had an effect on genes or proteins related to this pathway. Accordingly, we hypothesized that JAK-STAT signaling pathway-mediated EMT abnormalities play an important role in the pathogenesis of CAG, and that Yiqi Huayu Jiedu Decoction can play a role in blocking CAG "inflammation-cancer" transformation by regulating this pathway. In order to confirm the hypothesis, it is proposed to investigate the mechanism of this pathway in the pathogenesis of CAG and the intervention of Yiqi Huayu Jiedu decoction by combining inhibition and over expression in vivo and vitro, and to further investigate its mechanism by screening out the active ingredients that regulating this pathway through network pharmacology, molecular docking and PEAQ-ITC. The research provides a modern scientific basis for the treatment of CAG with Yiqi Huayu Jiedu Decoction, and provides ideas and a preliminary basis for the development of new Chinese medicine for delaying, reversing and preventing gastric precancerous lesions.