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中国糖尿病肾阴虚证患者的代谢组学与蛋白质组学整合研究。

An integrated metabonomic and proteomic study on Kidney-Yin Deficiency Syndrome patients with diabetes mellitus in China.

作者信息

Jiang Ning, Liu Hong-fang, Li Si-di, Zhou Wen-xia, Zhang Yong-xiang, Zhang Qi, Yan Xian-zhong

机构信息

Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.

Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100050, China.

出版信息

Acta Pharmacol Sin. 2015 Jun;36(6):689-98. doi: 10.1038/aps.2014.169. Epub 2015 May 4.

Abstract

AIM

To investigate specific changes in metabolites and proteins of Kidney-Yin Deficiency Syndrome (KYDS) patients with diabetes mellitus (DM) in China.

METHODS

KYDS (n=29) and non-KYDS (n=23) patients with DM were recruited for this study. The KYDS was diagnosed by two senior TCM clinicians separately. The metabonomic and proteomic profiles of the patients were assessed using a metabonomic strategy based on NMR with multivariate analysis and a proteomic strategy based on MALDI-TOF-MS, respectively.

RESULTS

Eighteen upregulated peptides and thirty downregulated peptides were observed in the plasma of the KYDS patients. Comparing the proteomic profiles of the KYDS and non-KYDS groups, however, no significantly differentially expressed peptides were found. At the same time, major metabolic alterations were found to distinguish the two groups, including eight significantly changed metabolites (creatinine, citrate, TMAO, phenylalanine, tyrosine, alanine, glycine and taurine). The levels of creatinine, citrate, TMAO, phenylalanine and tyrosine were decreased, whereas the levels of alanine, glycine and taurine were increased in the KYDS patients. These biochemical changes were found to be associated with alterations in amino acid metabolism, energy metabolism and gut microflora.

CONCLUSION

The identification of distinct expression profiles of metabolites and signaling pathways in KYDS patients with DM suggests that there are indeed molecular signatures underlying the principles of 'Syndrome Differentiation' in traditional Chinese medicine.

摘要

目的

研究中国糖尿病(DM)肾阴虚证(KYDS)患者代谢物和蛋白质的特定变化。

方法

本研究招募了29例KYDS和23例非KYDS的DM患者。KYDS由两名资深中医临床医生分别诊断。分别采用基于核磁共振(NMR)的代谢组学策略结合多变量分析和基于基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)的蛋白质组学策略评估患者的代谢组学和蛋白质组学特征。

结果

在KYDS患者血浆中观察到18种上调肽和30种下调肽。然而,比较KYDS组和非KYDS组的蛋白质组学特征,未发现明显差异表达的肽。同时,发现主要的代谢改变可区分两组,包括8种显著变化的代谢物(肌酐、柠檬酸、氧化三甲胺、苯丙氨酸、酪氨酸、丙氨酸、甘氨酸和牛磺酸)。KYDS患者中肌酐、柠檬酸、氧化三甲胺、苯丙氨酸和酪氨酸水平降低,而丙氨酸、甘氨酸和牛磺酸水平升高。这些生化变化与氨基酸代谢、能量代谢和肠道微生物群的改变有关。

结论

DM患者肾阴虚证中代谢物和信号通路独特表达谱的鉴定表明,中医“辨证论治”原则确实存在分子特征。

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