目的 通过非靶向代谢组学技术结合生物通路分析（ingenuity pathway analysis，IPA）探讨益胃饮干预胃癌前病变的潜在作用机制。方法 采用N-甲基-N'-硝基-N-亚硝基胍（MNNG）建立胃癌前病变大鼠模型，采用超高效液相色谱-四级杆飞行时间质谱（UPLC-Q-TOF/MS）检测并表征大鼠血清代谢物，筛选模型组和益胃饮组大鼠血清中具有显著变化的代谢物，并通过IPA软件预测其潜在作用靶点与机制。结果 益胃饮可有效干预大鼠胃癌前病变进程；胃癌前病变模型大鼠血清中有23个代谢物有显著变化（P<0.05），益胃饮可显著回调其中13个代谢物趋于正常水平（P<0.05），主要涉及不饱和脂肪酸的生物合成，缬氨酸、亮氨酸、异亮氨酸的生物合成，鞘脂代谢，花生四烯酸代谢，类固醇激素合成等代谢途径；益胃饮干预胃癌前病变与抑制体内皮素-1（ET-1）和白介素-8（IL-8）信号途径密切相关。结论 益胃饮可通过回调花生四烯酸代谢等代谢途径和抑制ET-1、IL-8信号传导途径改善炎性环境，从而抑制胃癌前病变进程。

Objective To study the potential mechanisms of Yiwei Decoction on intervening gastric precancerous lesions by using metabolomics technology combined with ingenuity pathway analysis (IPA). Methods Gastric precancerous lesion rat model induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was established and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was utilized to detect and characterize rat serum metabolites. Metabolites with significant changes in model group and Yiwei Decoction group were screened out; The IPA software was used to analyze the potential targets and mechanisms. Results Yiwei Decoction effectively interfered with the progress of gastric precancerous lesions. A total of 23 metabolites in the serum of gastric precancerous lesion rat model were significantly changed (P<0.05), 13 metabolites were significantly regulated to normal level in Yiwei Decoction group (P<0.05), the metabolic pathways mainly involved in the biosynthesis of unsaturated fatty acids, biosynthesis of valine, leucine and isoleucine, sphingolipid metabolism, arachidonic acid metabolism and steroid hormone synthesis, etc. The effect of Yiwei Decoction on intervening with the progression of gastric precancerous lesions was related to the inhibition of ET-1 and IL-8 signaling pathway. Conclusion Yiwei Decoction can inhibit the progress of gastric precancerous lesions and improve the inflammatory environment by regulating arachidonic acid metabolism and inhibiting ET-1 and IL-8 signaling pathways.

R285.5

国家自然科学基金面上项目（81973654）；浙江省基础公益研究计划项目（LGD19C040005）