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代谢组学研究干地黄胶囊对糖尿病肾病的保护作用。

Metabolomic study of the protective effect of Gandi capsule for diabetic nephropathy.

机构信息

School of Pharmacy, Second Military Medical University, Shanghai, China.

Department of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Chem Biol Interact. 2019 Dec 1;314:108815. doi: 10.1016/j.cbi.2019.108815. Epub 2019 Sep 6.

Abstract

Diabetic nephropathy (DN) is the one of the leading causes of end-stage renal disease (ESRD) in clinical. However, it is still lack of accurate biomarkers and effective methods for diagnosing and curing DN. Therefore, there is an urgent need to develop a definite strategy for the identification of reliable and versatile biomarkers for risk assessment of DN and search for therapeutic approaches that can effectively attenuate DN progression. Treatment with Gandi capsule (GDC) not only decreased the levels of urinary albumin excretion, but also increased the levels of estimated glomerular filtration rate (eGFR), indicating that it produces a renal protective effect on diabetic nephropathy. Based on metabolomics investigation including UHPLC-MS analysis and multivariate statistical analysis, sixteen disordered metabolites were screened out and considered as potential biomarkers corresponding to DN, which were mostly improved and partially returned to normalcy in GDC treatment group. Therefore, it was suggested that GDC was a promising therapeutic agent against DN. The underlying mechanisms of GDC attenuating the development of DN may be improving abnormal metabolic disorders by retrieving the imbalance of glycine metabolism, tryptophan metabolism, valine, leucine and isoleucine degradation, purine metabolism, nitrotoluene degradation, phenylalanine metabolism, fatty acid metabolism, tyrosine metabolism and bile acid metabolism pathways. The data obtained in this study may provide key clues to enhance our understanding of the metabolic mechanism of DN and shed new insights into the therapeutic mechanism of GDC.

摘要

糖尿病肾病(DN)是临床终末期肾病(ESRD)的主要原因之一。然而,目前仍然缺乏用于诊断和治疗 DN 的准确生物标志物和有效方法。因此,迫切需要制定明确的策略,以识别可靠和通用的生物标志物,用于评估 DN 的风险,并寻找可有效减缓 DN 进展的治疗方法。甘地胶囊(GDC)治疗不仅降低了尿白蛋白排泄水平,而且增加了估算肾小球滤过率(eGFR)水平,表明其对糖尿病肾病具有肾脏保护作用。基于包括 UHPLC-MS 分析和多变量统计分析在内的代谢组学研究,筛选出了 16 个紊乱的代谢物,并将其视为与 DN 相关的潜在生物标志物,这些标志物在 GDC 治疗组中得到了改善和部分恢复正常。因此,GDC 被认为是一种有前途的治疗 DN 的药物。GDC 减轻 DN 发展的潜在机制可能是通过恢复甘氨酸代谢、色氨酸代谢、缬氨酸、亮氨酸和异亮氨酸降解、嘌呤代谢、硝基甲苯降解、苯丙氨酸代谢、脂肪酸代谢、酪氨酸代谢和胆酸代谢途径的失衡来改善异常代谢紊乱。本研究获得的数据可能为增强我们对 DN 代谢机制的理解提供关键线索,并为 GDC 的治疗机制提供新的见解。

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