本文選題：代謝組學(xué) + 核磁共振�。� 參考：《分析化學(xué)》2017年09期

【摘要】：N-乙酰半胱氨酸(NAC)有減輕造影劑引發(fā)腎損傷的作用,但其作用機(jī)制尚未明確。本研究采用基于1H NMR的代謝組學(xué)方法,結(jié)合正交偏最小二乘法判別分析(OPLS-DA),在NAC保護(hù)下對慢性腎衰大鼠給藥造影劑釓-二乙三胺五乙酸(Gd-DTPA),通過分析大鼠尿液中內(nèi)源性代謝物的變化,研究了NAC對慢性腎衰大鼠的保護(hù)機(jī)制。結(jié)果表明,慢性腎衰大鼠能量代謝、尿素循環(huán)等代謝通路發(fā)生紊亂。給藥Gd-DTPA后,大鼠尿液中膽堿、N-氧三甲胺、鄰羥基苯乙酸苯酯、對羥基苯乙酸苯酯、馬尿酸、甘氨酸、煙酸、牛磺酸減少,尿囊素增加;而在NAC保護(hù)下相關(guān)代謝產(chǎn)物向模型組的恢復(fù),說明NAC對Gd-DTPA引發(fā)的大鼠腸道細(xì)菌代謝、肝線粒體代謝、犬尿氨酸代謝紊亂及氧化損傷具有一定修復(fù)作用。NAC對尿素循環(huán)代謝的改善可能減輕大鼠體內(nèi)的腎損傷,而其對細(xì)胞中谷胱甘肽的補(bǔ)充可能減輕Gd-DTPA造成的氧化損傷。
[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.
【作者單位】： 中國科學(xué)院長春應(yīng)用化學(xué)研究所;中國科學(xué)院大學(xué);
【基金】：國家自然科學(xué)基金項(xiàng)目(No.21305134)資助~~
【分類號】：O657.2;R965

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