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六价铬中毒致肉鸡肝损伤的代谢组学分析。

Metabonomic analysis of the hepatic injury suffer from hexavalent chromium poisoning in broilers.

机构信息

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, P.R. China.

College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.

出版信息

Environ Sci Pollut Res Int. 2019 Jun;26(18):18181-18190. doi: 10.1007/s11356-019-05075-4. Epub 2019 Apr 29.

Abstract

Chromium is used in daily life and has a wide range of functions. It plays an important role in protein synthesis and carbohydrate and lipid metabolism. Chromium is found in trivalent Cr(III) and hexavalent Cr(VI) form; Cr(III) is relatively stable and intimately participates with many phenomena of metabolisms. Whereas, Cr(VI) is toxic, which results in growth inhibition and leading to changes in components of antioxidant systems as well as secondary metabolites. However, the molecular mechanism that is involved in Cr (VI)-induced hepatotoxicity is still unclear. For this purpose, 40 chickens were randomly assigned into two groups: the normal group (feeding the basic diet and clear water), the chromium group (16%LD, 74.24 mg/kg/day KCrO ). The samples were subjected to pathological examination and UHPLC-QE-MS non-target metabolomics method for metabolomics analysis of broiler liver using principal component analysis (PCA) and partial least squares discriminant analysis (OPLS-DA). The central venous cells of the broiler liver in the chromium poisoning group showed turbidity and flaky necrosis, nuclear condensation, nuclear rupture, and even nuclear dissolution. The differential metabolite analysis between the chromium poisoning and the control group showed that 32 differential metabolites were upregulated and 15 were downregulated in positive ion mode. Whereas,17 differential metabolites were downregulated, and 35 were downregulated in negative ion mode (P ≤ 0.05). The potential marker substances are oleic acidamide, farnesylacetone, betaine, taurine, choline, and galactinol. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the lipid metabolism, carbohydrate metabolism, nucleotide metabolism, amino acid metabolism, energy metabolism, membrane transport, digestive system, and nervous system were the most important metabolic pathways in the liver. This study provides a theoretical basis for the future understanding of the pathogenesis of chromium poisoning and a new insight of the subsequent molecular mechanism of chromium hepatotoxicity.

摘要

铬在日常生活中被广泛应用,具有多种功能。它在蛋白质合成以及碳水化合物和脂质代谢中发挥着重要作用。铬有三价 Cr(III) 和六价 Cr(VI) 两种形式存在;Cr(III) 相对稳定,密切参与许多代谢现象。而 Cr(VI) 则具有毒性,会导致生长抑制,并导致抗氧化系统成分和次生代谢物发生变化。然而,Cr(VI) 诱导的肝毒性的分子机制尚不清楚。为此,将 40 只鸡随机分为两组:正常组(喂养基础日粮和清水),铬组(16%LD,74.24mg/kg/d KCrO )。对样本进行病理学检查,并采用 UHPLC-QE-MS 非靶向代谢组学方法对肉鸡肝脏进行代谢组学分析,采用主成分分析(PCA)和偏最小二乘判别分析(OPLS-DA)。铬中毒组肉鸡肝中央静脉细胞出现混浊和片状坏死、核浓缩、核破裂,甚至核溶解。铬中毒组与对照组的差异代谢物分析显示,正离子模式下有 32 个差异代谢物上调,15 个差异代谢物下调;负离子模式下有 17 个差异代谢物下调,35 个差异代谢物下调(P≤0.05)。潜在的标记物质是油酰胺、法呢基丙酮、甜菜碱、牛磺酸、胆碱和半乳糖醇。此外,京都基因与基因组百科全书(KEGG)通路显示,脂质代谢、碳水化合物代谢、核苷酸代谢、氨基酸代谢、能量代谢、膜转运、消化系统和神经系统是肝脏中最重要的代谢途径。本研究为今后了解铬中毒的发病机制提供了理论依据,并为铬肝毒性的后续分子机制提供了新的见解。

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