乙酰氨基酚对小鼠与人胚胎肝细胞毒性的microRNA生物标志物比较研究

发布时间：2018-04-19 22:38

本文选题：药理学 + 对乙酰氨基酚　；参考：《中国科技论文》2015年24期

【摘要】：为探索肝损伤时miRNA的变化特点及其作为潜在生物标志物在细胞水平的跨种属特性,研究以对乙酰氨基酚(acetaminophen,APAP)为模式药物,在胚胎肝细胞上建立不同程度的细胞毒模型。采用实时荧光定量PCR的方法检测人胚胎肝细胞CCC-HEL-1和小鼠胚胎肝细胞BNL CL.2 2个种属细胞中17个miRNA在药物作用下的表达变化,并进一步分析小鼠胚胎肝细胞BNL CL.2在APAP作用不同时间后miRNA的表达变化情况。研究发现:在APAP 3个毒性剂量(IC25、IC50和IC75)作用下,17个miRNA中,超过70%的miRNA在2个种属胚胎肝细胞上表达变化趋势一致,具有跨种属的特性,特别是miR-29b在2个种属的胚肝细胞系及3个毒性剂量作用下都明显上调;在BNL CL.2细胞上,APAP作用3、6、12、24、36h后,选取的4个miRNA的表达变化具有明显时间依赖性。研究表明:miRNA作为药源性肝损伤跨种属的生物标志物,具有巨大的潜在应用价值;其中miR-29b有望成为潜在的早期指示APAP肝毒性的跨种属生物标志物。
[Abstract]:In order to explore the characteristics of miRNA during liver injury and its cross-species characteristics at cell level as a potential biomarker, acetaminophenophenol acetaminophenol (acetaminophenol) was used as a model drug to establish cytotoxic models in embryonic liver cells. The expression of miRNA in human fetal hepatocytes (CCC-HEL-1) and mouse embryonic hepatocytes (BNL CL.2) was detected by real-time fluorescence quantitative PCR. The expression of BNL CL.2 in mouse embryonic liver cells was analyzed after APAP treatment for different time. It was found that under the action of IC25 IC50 and IC75, more than 70% of miRNA in 17 miRNA had the same trend of expression in fetal hepatocytes of 2 species, and had the characteristics of interspecies. In particular, miR-29b was upregulated in two species of embryonic liver cell lines and three toxic doses, and the expression changes of 4 miRNA in BNL CL.2 cells were time-dependent. As a biomarker of drug-induced liver injury, miR-29b is expected to be a potential biomarker to indicate the liver toxicity of APAP in the early stage.
【作者单位】：浙江大学药学院;
【基金】：高等学校博士学科点专项科研基金资助项目(20120101120137)
【分类号】：R965

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