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目的 研究Z2 4染毒大鼠血浆的代谢表型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大鼠连续经口染毒 0、60、13 0和 2 0 0mg/kgZ2 45d后收集血浆 ,测定1 HNMR谱 ,并进行血浆生化指标测定和肝脏组织病理学检查。结果 2 0 0mg/kg组大鼠血浆丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)及总胆红素 (TbiL)分别升高了 14 8 4%、14 0 %和 10 9 8% ;13 0和 2 0 0mg/kg组均出现不同程度的肝脏炎症和坏死。血浆1 HNMR谱偏最小乘方分析 (PLS DA)发现在不同染毒条件下 ,各组动物的代谢谱各不相同 ,与肝脏病理和血浆生化改变相一致 ,并且其敏感性优于常规毒理学检测指标。结论 大鼠血浆1 HNMR代谢谱与Z2 4毒作用强度密切相关 ,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 investigate the changes of plasma phenotype in Z2 4 -treated rats and its correlation with histopathology and blood biochemical parameters and to explore the application of metabolomics in the early screening of drug toxicity. Methods Wistar rats were continuously orally exposed to 0, 60, 13 and 200 mg / kg Z2 45 days later. The plasma was collected and the 1 HNMR spectra were measured. The plasma biochemical indexes and liver histopathological examination were also performed. Results Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TbiL) increased by 14 8 4%, 140% and 10 9 8 in the 200 mg / kg group %; Different degrees of hepatic inflammation and necrosis occurred in the 13 0 and 200 mg / kg groups. Plasma 1 HNMR spectral PLS analysis showed that the metabolites of each group were different under different exposure conditions, consistent with liver pathology and plasma biochemical changes, and their sensitivity was superior to that of conventional toxicology Detection Indicator. Conclusions The 1 HNMR metabolite profile in plasma of rats is closely related to the intensity of Z2 4 toxicity. Metabonomic analysis is a promising method for early screening of drug toxicity in vivo