Metabolomic study of the protective effect of Gandi capsule for diabetic nephropathy
Metabolomic study of the protective effect of Gandi capsule for diabetic nephropathy
复制标题
甘地胶囊对糖尿病肾病保护作用的代谢组学研究
DOI：
10.1016/j.cbi.2019.108815
复制
发表时间：
2019-12-01
影响因子：
5.1
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Liu, Yue;Chen, Xiaofei;Zhang, Jian
糖尿病肾病（DN）是临床上终末期肾病（ESRD）的主要病因之一。然而，目前尚缺乏准确的DN生物标志物和有效的DN诊断和治疗方法。因此，有一个迫切需要开发一个明确的战略，确定可靠的和通用的生物标志物的风险评估DN和寻找治疗方法，可以有效地减缓DN的进展。甘迪胶囊（GDC）治疗不仅降低了尿白蛋白排泄水平，而且提高了估计肾小球滤过率（eGFR）水平，表明其对糖尿病肾病产生肾脏保护作用。基于代谢组学研究，包括UHPLC-MS分析和多变量统计分析，筛选出16种代谢紊乱的代谢物，并认为这些代谢紊乱的代谢物是与DN相对应的潜在生物标志物，GDC治疗组中这些代谢紊乱的代谢物大部分得到改善，部分恢复正常。因此，GDC是一种很有前途的DN治疗药物。GDC减轻DN发生发展的机制可能是通过纠正甘氨酸代谢、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、酪氨酸代谢和胆汁酸代谢途径的失衡来改善异常代谢紊乱。本研究的结果为深入了解DN的代谢机制提供了重要线索，并为探讨GDC的治疗机制提供了新的思路。
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.