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基于 UPLC-MS 的代谢组学方法结合模式识别技术研究原发性痛经患者血浆和尿液中的生物化学变化。

Metabolomic study of biochemical changes in the plasma and urine of primary dysmenorrhea patients using UPLC-MS coupled with a pattern recognition approach.

机构信息

Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210046, P.R. China.

出版信息

J Proteome Res. 2013 Feb 1;12(2):852-65. doi: 10.1021/pr300935x. Epub 2013 Jan 18.

Abstract

Primary dysmenorrhea (PD) is characterized by painful menstrual cramps without any organic pathology and has a prevalence of up to 90% in adolescents. Recent advances in its etiology and pathogenesis are providing more speculative hypotheses focused on integral systems. Using a targeted tandem mass spectrometry (MS/MS)-based metabolomic platform, we explored the changes of metabolic profiling in plasma/urine simultaneously between PD patients and healthy controls before and after a 3-month herbal medicine (namely Shaofu Zhuyu formula concentrated-granule, SFZYFG) therapy. To detect and identify potential biomarkers associated with PD and SFZYFG treatment, we also performed a combined UPLC-QTOF-MS/MS-based metabolomic profiling of the plasma/urine samples, indicating a further deviation of the patients' global metabolic profile from that of controls. The total thirty-five metabolites (nineteen in plasma and sixteen in urine), up-regulated or down-regulated (p < 0.05 or 0.01), were identified and contributed to PD progress. These promising identified biomarkers underpinning the metabolic pathway including sphingolipid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism are disturbed in PD patients, which were identified by using pathway analysis with MetPA. Twenty-four altered metabolites and fourteen biochemical indicators were restored back to the control-like level after the treatment of SFZYFG and could be potential biomarkers for monitoring therapeutic efficacy. These findings may be promising to yield a valuable insight into the pathophysiology of PD and to advance the approaches of treatment, diagnosis, and prevention of PD and related syndromes.

摘要

原发性痛经(PD)的特征是月经期间出现疼痛性痉挛,但没有任何器质性病变,在青少年中的患病率高达 90%。其病因和发病机制的最新进展提供了更多针对整体系统的推测性假说。我们使用靶向串联质谱(MS/MS)代谢组学平台,在 PD 患者和健康对照组之间,在 3 个月的草药(即少腹逐瘀配方浓缩颗粒,SFZYFG)治疗前后,同时探索了血浆/尿液代谢谱的变化。为了检测和鉴定与 PD 和 SFZYFG 治疗相关的潜在生物标志物,我们还对血浆/尿液样本进行了基于 UPLC-QTOF-MS/MS 的代谢组学联合分析,表明患者的整体代谢谱与对照组进一步偏离。共鉴定出 35 种代谢物(血浆中 19 种,尿液中 16 种),上调或下调(p<0.05 或 0.01),这些代谢物与 PD 进展有关。这些有希望的生物标志物支持包括鞘脂代谢、类固醇激素生物合成和甘油磷脂代谢在内的代谢途径,它们在 PD 患者中受到干扰,这是通过使用 MetPA 进行途径分析来确定的。SFZYFG 治疗后,24 种代谢物和 14 种生化指标恢复到对照水平,可作为监测治疗效果的潜在生物标志物。这些发现可能有助于深入了解 PD 的病理生理学,并推进 PD 及相关综合征的治疗、诊断和预防方法。

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