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目的 研究Z2 4染毒大鼠尿液代谢组学的改变及其与组织病理和血液生化指标的相关性 ,探讨代谢组学在药物毒性早期筛选中的应用。方法Wistar大鼠连续经口给予Z2 4 6 0 ,130及 2 0 0mg·kg- 1,连续 5d后收集 2 4h尿液 ,测定核磁共振([1H]NMR)谱 ,并进行血浆生化指标测定和肝脏组织病理学检查。结果 Z2 4 2 0 0mg·kg- 1组大鼠血浆谷丙转氨酶、谷草转氨酶和总胆红素分别升高14 8% ,14 0 %和 110 % ;130和 2 0 0mg·kg- 1组均有不同程度的肝脏炎症和坏死。 [1H]NMR谱主成分分析发现各组在不同染毒条件下的代谢状态可相互区分 ,与肝脏病理和血浆生化改变相一致。结论 大鼠尿液 [1H]NMR代谢谱与Z2 4毒性作用强度密切相关 ,代谢组学分析是一种有良好发展前景的体内药物毒性早期筛选的方法。
Objective To study the changes of urinal metabolomics and its relationship with histopathology and blood biochemical parameters in Z2 4 -treated rats and to explore the application of metabolomics in the early screening of drug toxicity. Methods Wistar rats were continuously given Z2 460, 130 and 200 mg · kg-1 orally for 24 hours. Urine was collected for 5 days and their nuclear magnetic resonance (1H) NMR spectra were measured. Liver histopathology examination. Results Plasma alanine aminotransferase, aspartate aminotransferase and total bilirubin in Z2 420 mg · kg -1 group were increased by 14 8%, 14 0% and 110%, respectively. Both 130 and 200 mg · kg -1 group There are different degrees of liver inflammation and necrosis. The principal component analysis of [1H] NMR spectra showed that the metabolic status of each group under different exposure conditions could be distinguished from each other, which was consistent with liver pathology and plasma biochemical changes. Conclusion The metabolite spectrum of [1H] NMR in rat urine is closely related to the intensity of Z2 4 toxicity. Metabolomics analysis is a promising method for the early screening of drug toxicity in vivo.