铁皮石斛水提物对胃癌前病变作用的尿液代谢组学分析

目的:研究铁皮石斛水提物对胃癌前病变大鼠尿液内源性代谢物的影响。方法:将Wistar大鼠随机分为正常组、铁皮石斛水提物(DOE)组、模型组及N-甲基-N'-硝基-N-亚硝基胍(MNNG)+DOE低、中、高剂量组。DOE组和MNNG+DOE低、中、高剂量组大鼠预防性给予DOE 2周后开始给予自由饮100 mg·L-1MNNG水溶液,边给药边造模,并在前6周,每3 d灌胃给予10%Na Cl 1 m L诱导。造模7个月后代谢笼收集大鼠尿液并处死大鼠取胃组织。采用UPLC-Q-TOF-MS检测大鼠尿液代谢谱的变化。结果:对比各组胃组织病理结果发现DOE能够减少肠化生,使病理程度停留在轻度至中度异型增生和轻度肠化生阶段。在正、负离子模式下分别筛选出6个和15个差异性标志化合物;代谢产物主要与卟啉代谢、色氨酸代谢、叶酸和蝶呤生物合成代谢、半乳糖代谢和花生四烯酸代谢有关,其中以卟啉代谢最为相关。结论:DOE能够阻断胃癌前病变的恶化,其机制可能与卟啉代谢、色氨酸代谢、叶酸和蝶呤生物合成代谢、半乳糖代谢和花生四烯酸代谢有关。

Urine Metabolomics Analysis of Effect of Dendrobii Officinalis Caulis Aqueous Extract on Gastric Precancerous Lesions

Objective: To study on the effect of Dendrobii Officinalis Caulis aqueous extract on endogenous metabolites in urine of rats with gastric precancerous lesions. Method: Wistar rats were randomly divided into normal group, Dendrobii Officinalis Caulis aqueous extract(DOE) group, model group, N-methyl-N''-nitro-N-nitrosoguanidine(MNNG) +DOE groups at low, middle and high dosages.After 2 weeks of prophylactic administration of DOE, 100 mg·L^-1 MNNG aqueous solution was given to the free drink, and the model was made as the drug was administered.In addition, in the first 6 weeks, rats were given 1 mL of 10% NaCl every 3 days for inducing gastric precancerous lesions.After 7 months of modeling, the rat urine was collected and the rats were sacrificed for gastric tissue.UPLC-Q-TOF-MS was used to detect the changes of urine metabolic profile in rats. Result: By comparing the histopathological results of gastric tissues in each group, it was found that DOE could reduce the intestinal metaplasia and make the pathological degree stay in the stage of mild-moderate dysplasia and mild intestinal metaplasia.In positive and negative ion modes, 6 and 15 differential marker compounds were screened, respectively.Metabolites were mainly related to porphyrin metabolism, tryptophan metabolism, folic acid and pterin biosynthetic metabolism, galactose metabolism and arachidonic acid metabolism, of which porphyrin metabolism was the most relevant. Conclusion: DOE can block the progression of gastric precancerous lesions, its mechanism may be related to porphyrin metabolism, tryptophan metabolism, folic acid and pterin biosynthesis, galactose metabolism and arachidonic acid metabolism.