基于1H-NMR代谢组学分析山楂不同炮制品对食积症的影响

目的:采用~1H-NMR技术的血清代谢组学方法,并结合传统生化指标分析,研究炮制对山楂促消化作用的影响。方法:实验动物喂饲特制高蛋白、高热量饲料复制食积模型,以小鼠小肠推进率和大鼠胃肠道激素水平作为药效学指标,应用~1H-NMR测定大鼠血清,结合多元统计分析方法对比给予大鼠净山楂、炒山楂、焦山楂后血清代谢物的变化,比较各炮制品对食积模型大鼠的治疗作用。结果:山楂各炮制品组对于食积因素引起的小鼠肠推进障碍及胃肠激素分泌紊乱均有改善作用,且以焦山楂组改善效果最为显著。大鼠血清代谢组学结果显示,模型组与空白组存在明显的代谢差异,根据S-plot图的变量重要性投影(VIP)值、单因素ANOVA以及受试者工作特征曲线(ROC曲线)下的面积(AUC)筛选出3-羟基丁酸,甘油磷酰胆碱(GPC),N-乙酰糖蛋白,O-乙酰糖蛋白,氧化三甲胺,丙氨酸,乙酸,谷氨酸,谷氨酰胺,肌酸,亮氨酸,乳酸,葡萄糖共13个与食积相关的生物标志物。比较给药后山楂各炮制品组引起的代谢变化,发现焦山楂组对O-乙酰糖蛋白、谷氨酰胺和GPC的回调趋势更接近空白组,其余代谢产物组成与净山楂组和炒山楂组基本一致。结论:山楂炮制后消食导滞作用存在一定差异,焦山楂改善食积疗效最为显著,可能主要通过调节胃肠动力障碍及能量代谢等发挥作用。

Effect of Different Processed Products of Crataegi Fructus on Dyspepsia by 1H-NMR Metabonomics

Objective:The effect of processing on promoting digestion of Crataegi Fructus was investigated by the method of serum metabonomics based on ¹H-NMR and the analysis of traditional biochemical indexes. Method:The dyspepsia model was induced by high protein and calorie diet. The small intestine propulsive rate in mice and the hormone level in rat gastrointestinal tract were used as pharmacodynamic indexes. After administration of Crataegi Fructus, fried and charred Crataegi Fructus, the changes of serum metabolites were analyzed by ¹H-NMR technique combined with multivariate statistical analysis, so as to compare the therapeutic effects of each processed products on rats with dyspepsia model. Result:Each processed products group of Crataegi Fructus could improve the ability of intestinal propulsion and gastric emptying, especially in charred Crataegi Fructus group, caused by dyspepsia. The serum metabonomics proved that there were significant metabolic differences between the model group and the blank group. A total of 13 biomarkers related to dyspepsia, covering 3-hydroxybutyric acid, glycerophosphoryl choline (GPC), N-acetylglycoprotein, O-acetylglycoprotein, trimethylamine oxide (TMAO), alanine, acetic acid, glutamic acid, glutamine, creatine, leucine, lactic acid and glucose, were screened on the grounds of VIP value of S-plot, single factor ANOVA and area under receiver operating characteristic curve (ROC curve) (AUC). The metabolite composition of each administration group was the same except that the callback tendency of O-acetylglycoprotein, glutamine and GPC in charred Crataegi Fructus group was closer to that in the blank group. Conclusion:There are differences in the effect of promoting digestion to eliminate stagnation among processed products of Crataegi Fructus, charred Crataegi Fructus is more effective in improving dyspepsia, which may play a role in regulating gastrointestinal motility and energy metabolism.