<i>N</i>-乙酰半胱氨酸保护下给药钆-二乙三胺五乙酸后慢性肾衰大鼠的尿液代谢组学研究

引用本文: 万传玲, 薛蓉, 湛游洋, 李晓晶, 裴奉奎. N-乙酰半胱氨酸保护下给药钆-二乙三胺五乙酸后慢性肾衰大鼠的尿液代谢组学研究[J]. 分析化学, 2017, 45(9): 1271-1277. doi: 10.11895/j.issn.0253-3820.170307 shu

Citation: WAN Chuan-Ling, XUE Rong, ZHAN You-Yang, LI Xiao-Jing, PEI Feng-Kui. Urinary Metabonomic Study on N-Acetylcysteine-Protected Rats with Chronic Renal Failure from Gd-Diethylenetriamine Pentaacetic Acid Administration[J]. Chinese Journal of Analytical Chemistry, 2017, 45(9): 1271-1277. doi: 10.11895/j.issn.0253-3820.170307 shu

N-乙酰半胱氨酸保护下给药钆-二乙三胺五乙酸后慢性肾衰大鼠的尿液代谢组学研究

1.
中国科学院长春应用化学研究所, 长春 130022;2 中国科学院大学, 北京 100049
基金项目:
本文系国家自然科学基金项目（No.21305134）资助

摘要: N-乙酰半胱氨酸（NAC）有减轻造影剂引发肾损伤的作用，但其作用机制尚未明确。本研究采用基于¹H NMR的代谢组学方法，结合正交偏最小二乘法判别分析（OPLS-DA），在NAC保护下对慢性肾衰大鼠给药造影剂钆-二乙三胺五乙酸（Gd-DTPA），通过分析大鼠尿液中内源性代谢物的变化，研究了NAC对慢性肾衰大鼠的保护机制。结果表明，慢性肾衰大鼠能量代谢、尿素循环等代谢通路发生紊乱。给药Gd-DTPA后，大鼠尿液中胆碱、N-氧三甲胺、邻羟基苯乙酸苯酯、对羟基苯乙酸苯酯、马尿酸、甘氨酸、烟酸、牛磺酸减少，尿囊素增加；而在NAC保护下相关代谢产物向模型组的恢复，说明NAC对Gd-DTPA引发的大鼠肠道细菌代谢、肝线粒体代谢、犬尿氨酸代谢紊乱及氧化损伤具有一定修复作用。NAC对尿素循环代谢的改善可能减轻大鼠体内的肾损伤，而其对细胞中谷胱甘肽的补充可能减轻Gd-DTPA造成的氧化损伤。

关键词:

English

Urinary Metabonomic Study on N-Acetylcysteine-Protected Rats with Chronic Renal Failure from Gd-Diethylenetriamine Pentaacetic Acid Administration

1.
Changchun Institute of Applied Chemistry Chinese Academy of Sciences, Changchun 130022, China;2 University of Chinese Academy of Sciences, Beijing 100049, China
Received Date: 17 April 2017
Revised Date: 20 June 2017
Fund Project:
This work was supported by the National Natural Science Foundation of China (No.21305134).

Abstract: N-Acetylcysteine (NAC) protects rats administrated with gadolinium-based contrast agents from renal injury, however, the underlying mechanisms remain unclear. A 1H NMR-based metabolomics approach coupled with OPLS-DA (orthogonal projection to latent structure with discriminant analysis) was used to analyze the effect of NAC on urinary metabolic changes for Chronic Renal Failure Rats administrated with Gd-DTPA (Gd-Diethylenetriamine pentaacetic acid). Combined with univariate analysis of integral area, the significantly changed metabolites were selected to screen out the potential metabolic disturbances that induced by Gd-DTPA and NAC. These researches may attribute to study of the protective effect of NAC from renal failure induced by gadolinium-based contrast agents. The disturbance of energy metabolism, urea cycle and kynurenine metabolism were observed from the CRF group. Gd-DTPA caused the reduction of urinary choline, TMAO, o-HPA, p-HPA, hippurate, glycine, nicotinate and taurine accompanied with the elevation of allantoin. Metabonomic recovery in the NAC group was observed, which implied that NAC protects rats with chronic renal failure from Gd-DTPA induced disturbances of gut microbiota metabolism, liver mitochondria metabolism and kynurenine metabolism. The replenishment of glutathione in cells and the recovery of urea cycle that caused by NAC may protect rats from oxidative damage and renal injury.

Key words:

Metabonomics
/ Nuclear magnetic resonance
/ Chronic renal failure
/ Gd-diethylenetriamine pentaacetic acid
/ N-Acetylcysteine

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沈阳化工大学材料科学与工程学院沈阳 110142

N-乙酰半胱氨酸保护下给药钆-二乙三胺五乙酸后慢性肾衰大鼠的尿液代谢组学研究

English

Urinary Metabonomic Study on N-Acetylcysteine-Protected Rats with Chronic Renal Failure from Gd-Diethylenetriamine Pentaacetic Acid Administration

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

N-乙酰半胱氨酸保护下给药钆-二乙三胺五乙酸后慢性肾衰大鼠的尿液代谢组学研究

English

Urinary Metabonomic Study on N-Acetylcysteine-Protected Rats with Chronic Renal Failure from Gd-Diethylenetriamine Pentaacetic Acid Administration

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

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CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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