微囊藻毒素(MCLR),，作為一種肝毒素,，正在威脅著人類的公共衛(wèi)生安全。在體內(nèi),，肝臟是MCLR主要攻擊的器官,，然而具體代謝變化目前任然未知。近日,，中國科學院水生生物研究所謝平等研究人員在與上海敏芯信息科技公司的合作下,，通過對灌服MCLR的大鼠模型進行代謝組學的研究，向我們揭示了MCLR擾亂肝臟代謝的真面目,，此研究已經(jīng)刊登于國際雜志Journal of Proteome Research上,。
該研究小組通過核磁共振(NMR)的實驗平臺完成了代謝組學研究，同時利用液質(zhì)聯(lián)用技術(shù)(LC-ESI-MS)對肝臟MCLR,、谷胱苷肽與半胱氨酸軛合物進行定量,。
代謝組學研究表明，MCLR作用于肝臟,，導致酪氨酸合成與分解代謝明顯受到抑制,，三條膽堿相關(guān)代謝途徑被截斷，谷胱甘肽的消耗并且擾亂了核苷酸的合成,。即使是低劑量給予MCLR(0.04mg/kg),，雖在組織學上沒有明顯變化，但從代謝層面上說,，已經(jīng)能引起肝代謝的異常,。
代謝組學的研究結(jié)果在功能水平上為MCLR肝毒機制研究提供了新的觀點，同時也為以后關(guān)于微囊藻毒素威脅人類健康的評估及闡述打下了基礎,。(生物谷Bioon.com)
DOI: 10.1021/pr300685g
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Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-Based Metabonomic Study
Jun He †, Jun Chen *†, Laiyan Wu †‡, Guangyu Li †§, and Ping Xie *†
Microcystin-LR (MCLR), a potent hepatotoxin, is causing increased risks to public health. Although the liver is the main target organ of MCLR, the metabolic profiling of liver in response to MCLR in vivo remains unknown. Here, we comprehensively analyzed the metabolic change of liver and ileal flushes in rat orally gavaged with MCLR by 1H nuclear magnetic resonance (NMR). Quantification of hepatic MCLR and its glutathione and cysteine conjugates by liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS) was conducted. Metabonomics results revealed significant associations of MCLR-induced disruption of hepatic metabolisms with inhibition of nutrient absorption, as evidenced by a severe decrease of 12 amino acids in the liver and their corresponding elevation in ileal flushes. The hepatic metabolism signature of MCLR was characterized by significant inhibition of tyrosine anabolism and catabolism, three disrupted pathways of choline metabolism, glutathione exhaustion, and disturbed nucleotide synthesis. Notably, substantial alterations of hepatic metabolism were observable even at the low MCLR-treated group (0.04 mg/kg MCLR), although no apparent histological changes in liver were observed in the low- and medium-dosed groups. These observations offered novel insights into the microcystin hepatotoxic mechanism at a functional level, thereby facilitating further assessment and clarification of human health risk from MCs exposure.
