目的 采用核磁（¹H-NMR）代謝組學(xué)技術(shù)初步探討四氯化碳（CCl₄）致大鼠急性肝損傷后血清代謝物變化規(guī)律。方法 SD大鼠隨機(jī)分為空白、模型兩組，模型組ip 40% CCl₄植物油溶液造成急性肝損傷模型，空白組注射等體積的植物油，造模24 h后股動(dòng)脈取血，常規(guī)肝臟病理切片，取血前12 h禁食不禁水。比色法測(cè)定血清丙氨酸氨基轉(zhuǎn)移酶（ALT）含量，600 MHz NMR波譜儀分析血清中小分子代謝物代謝輪廓，并對(duì)數(shù)據(jù)進(jìn)行多元統(tǒng)計(jì)分析。結(jié)果 模型組中ALT的含量顯著升高，肝臟病理切片顯示模型組大鼠的肝組織內(nèi)形成很多空泡，肝細(xì)胞變大，壞死嚴(yán)重，有出血和大量中性粒細(xì)胞浸潤(rùn)；血清¹H-NMR代謝圖譜中共鑒定了20個(gè)代謝物，并確認(rèn)了6個(gè)與CCl₄致肝損傷相關(guān)的標(biāo)志物。結(jié)論 常規(guī)血生化指標(biāo)和肝病理切片結(jié)果與代謝組學(xué)的多元統(tǒng)計(jì)分析結(jié)果相一致，且代謝組學(xué)可發(fā)現(xiàn)引起肝損傷的代謝標(biāo)志物。

Objective The nuclear magnetic resonance (¹H-NMR) metabonomic technique is applied to study the change of serum metabolites in Sprague Dawley rats with CCl₄-induced acute liver injury. Methods The rats were randomly divided into control and model groups. The rats in the model group were ip injected with 40% CCl₄ solution of corn oil, while the rats in the control group were injected with the same amount of corn oil. The blood samples were collected from femoral artery after 24 h of CCl₄ treatment. The liver tissues were immediately removed and used for histopathological examination. The alanine aminotransferase (ALT) was determined using commercially available assay kits. The 600 MHz NMR spectrometer was used to analyze the metabolic profile of the small molecule metabolites in serum, and multivariate statistical analysis of the data was also conducted. Results The content of ALT in the model group was significantly increased. Histopathology of liver showed that there were many vacuoles and a large number of neutrophils infiltrating in the liver tissue of model group. The hepatic cells were necrotic and severely bleeding. Twenty metabolites were confirmed by NMR spectra, and six markers were affirmed to have associations with CCl₄-induced liver injury. Conclusion The results concluded by the multivariate statistical analysis of metabonomics are consistent with the conventional biochemical indicators and histopathology of liver. Furthermore, metabonomics could find markers which cause liver injury.

國(guó)家自然科學(xué)基金資助項(xiàng)目（31070295，31100244）