黄芪建中汤治疗大鼠慢性萎缩性胃炎的代谢组学研究

目的分析黄芪建中汤(Huangqi Jianzhong Decoction,HQJZ)对慢性萎缩性胃炎(CAG)大鼠血浆内源性代谢物紊乱的调控作用,阐明其对靶标的调控途径。方法以脱氧胆酸钠和氨水溶液交替饮用进行化学诱导,结合饥饱失常方法复制CAG大鼠模型。将大鼠随机分为对照组、模型组、阳性药(替普瑞酮)组和HQJZ高、中、低剂量组,连续4周ig给药。利用传统药效学指标(体质量、生化指标和组织病理学)评价HQJZ药效。用1H-NMR采集血浆代谢物数据,进行多元统计分析,寻找与HQJZ疗效相关的药效标志物。并结合偏最小二乘回归分析(PLS-RA)和Met PA筛选出与疗效最相关的代谢通路。结果 HQJZ可显著抑制CAG病变,与替普瑞酮作用相当。1H-NMR代谢组学找到18个与CAG密切相关的血浆代谢物。HQJZ可显著调节3-羟基丁酸、乳酸、醋酸、琥珀酸等10个代谢物的紊乱,通路分析显示精氨酸-脯氨酸代谢、甘油代谢和甘氨酸-丝氨酸-苏氨酸代谢为其治疗CAG的主要靶标途径。结论 HQJZ对CAG治疗作用的主要效应机制涉及其对能量平衡、免疫失调、炎症和和氧化应激的调节作用。

Metabonomics study on interventions of Huangqi Jianzhong Decoction against chronic atrophic gastritis in rats

Objective To address the protective role Huangqi Jianzhong Decoction (HQJZ) against chronic atrophic gastritis (CAG) in rats with metabolites in serum, and illuminate its regulative approaches to the targets.Methods CAG rat model was constructed by alternant administrations of ammonia solution and sodium deoxycholate, combined with the hunger disorder method. Rats were randomly separated into five groups:control group, model group, positive group (teprenone), low-dose group, medium-dose group, and high-dose group of HQJZ for continuous ig administration for four weeks. Body weight, biochemical indexes, and histopathological exam were used to evaluate the efficacy of HQJZ after the model replicated successfully. ¹H NMR-based metabonomics was employed to analyze the plasma metabolic features of HQJZ deviated from CAG rats. Partial least square regression analysis (PLS-RA) and MetPA analysis were utilized to explore the relevant pathways and the underlying mechanism involved in HQJZ against CAG.Results The pharmacodynamic results demonstrated that HQJZ possessed beneficial activities in treating CAG, which partially ascribed to the improvement of gastric PA and antioxidant system in vivo. A total of 18 plasma metabolites were selected as the potential biomarkers related to the development of CAG, 10 out of them including 3-hydroxybutyrate, lactate, acetate, succinate, etc. were significantly regulated by HQJZ. Three regulation pathways:arginine and proline metabolism, glycerolipid metabolism, and glycine, serine and threonine metabolism, were recognized to be the most relevant efficacy of HQJZ against CAG based on PLS-RA and MetPA analysis.Conclusion The efficacy of HQJZ against CAG were ascribed to the improvement of the pathological changes due to its regulation to the energy imbalance, excessive oxidative stress, immune disorders, as well as inflammation.