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

发布时间：2018-05-16 15:13

本文选题：代谢组学 + 核磁共振　；参考：《分析化学》2017年09期

【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。
[Abstract]:N- acetylcysteine (NAC) can attenuate renal injury induced by contrast agent, but its mechanism is not clear. In this study, a 1H NMR based metabolomics method was used. Combined with orthogonal partial least squares discriminant analysis, Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPAA), a contrast agent, was administered to rats with chronic renal failure (CRF) under the protection of NAC. The changes of endogenous metabolites in rat urine were analyzed. The protective mechanism of NAC on chronic renal failure (CRF) rats was studied. The results showed that energy metabolism, urea circulation and other metabolic pathways were disturbed in chronic renal failure rats. After administration of Gd-DTPA, the levels of choline N-oxomethylamine, o-hydroxyphenylacetate, p-hydroxyphenylacetate, hippuric acid, glycine, nicotinic acid, taurine were decreased and allantoin was increased. The recovery of related metabolites to the model group under the protection of NAC showed that NAC induced the metabolism of intestinal bacteria and hepatic mitochondria in rats induced by Gd-DTPA. The amelioration of urea cycle metabolism by NAC may alleviate the renal injury in rats, while the supplement of glutathione in the cells may alleviate the oxidative damage caused by Gd-DTPA.
【作者单位】：中国科学院长春应用化学研究所;中国科学院大学;
【基金】：国家自然科学基金项目(No.21305134)资助~~
【分类号】：O657.2;R965

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