穿山龙提取物抗急性痛风性关节炎的尿液代谢组学分析

目的:对急性痛风性关节炎大鼠给予穿山龙提取物后的尿液代谢组学进行研究,寻找相关的潜在生物标志物及相关代谢通路。方法:采用尿酸钠(MSU)诱导的急性痛风性关节炎大鼠模型,将SD大鼠40只随机分为空白组、穿山龙提取物组、模型组、穿山龙提取物干预组,每组10只。给药组灌胃给予穿山龙提取物,给药剂量0. 48 g·kg~(-1),每天1次,连续5 d,于末次给药后,收集大鼠尿液,运用UPLC-Q-TOF/MS结合模式识别方法分析,采用正、负离子扫描模式下电喷雾离子源,数据采集范围m/z 100～1 500,采用全扫描方式。结果:鉴别出了12个共同的潜在生物标志物,分别为肌氨酸,二甲基甘氨酸,脱氧胞苷,尿酸,5-HT,L-胱硫醚,4-吡哆酸,脱氧尿苷,褪黑激素,5-甲氧基色胺,富马酸和胞苷。与空白组比较,穿山龙提取物组中这12个潜在生物标志物均明显下调;与模型组比较,在穿山龙提取物干预组的潜在生物标志物中,有10个上调,2个下调,穿山龙提取物对肌氨酸,尿酸,L-胱硫醚,4-吡哆酸,脱氧尿苷,5-甲氧基色胺,胞苷,二甲基甘氨酸,褪黑激素,富马酸这10个标志物均表现出了纠正异常表达的趋势;与急性痛风性关节炎相关性最强的代谢通路为半胱氨酸和甲硫氨酸代谢、色氨酸代谢。结论:穿山龙提取物可能是通过促进半胱氨酸和甲硫氨酸代谢中胱硫醚向半胱氨酸的转化水平,上调色氨酸代谢中褪黑激素,实现对痛风性关节炎的防治作用。

Analysis on Urine Metabolomics of Dioscoreae Nipponicae Rhizoma Extract Against Acute Gouty Arthritis

Objective: To explore the effect of Dioscoreae Nipponicae Rhizoma extract (DNRe) on rats with acute gouty arthritis (AGA) based on urine metabolomics and to search for the related potential biomarkers and metabolic pathways. Method: Rat model of AGA induced by monosodium urate (MSU) was selected, 40 rats were randomly divided into the blank group (k), the DNRe group (g), the model group (m), and the DNRe treatment group (gm), with 10 rats in each group. The drug-administered group was administered with DNRe at a dose of 0.48 g·kg^-1 once a day for 5 days. The urine was gathered after the last administration, and analyzed with UPLC-Q-TOF/MS coupled with pattern recognition techniques, electrospray ionization (ESI) under positive and negative ion scanning mode was adopted, data collection range was m/z 100-1 500 with full scanning mode. Result: A total of 12 common potential biomarkers were identified as sarcosine, dimethylglycine, deoxycytidine, uric acid, 5-hydroxytryptamine (5-HT), L-cystathionine, 4-pyridoxic acid, deoxyuridine, melatonin, 5-methoxytryptamine, fumaric acid and cytidine. Compared with the blank group, the 12 potential biomarkers in the DNRe group were significantly down-regulated. Compare with the model group, 10 metabolites were up-regulated and 2 metabolites were down-regulated in the 12 potential biomarkers of the DNRe treatment group, the abnormal expression of 10 markers including sarcosine, uric acid, L-cystathionine, 4-pyridoxic acid, deoxyuridine, 5-methoxytryptamine, cytidine, dimethylglycine, melatonin, fumaric acid could be modulated by DNRe. The strongest metabolic pathways associated with AGA were cysteine and methionine metabolism, and tryptophan metabolism. Conclusion: The effect of DNRe on AGA may be related to the promotion of conversion level from cystathionine to cysteine in the cysteine and methionine metabolism, and the up-regulating melatonin level in tryptophan metabolism.