microRNA-122作为新药肝毒性早期评价标志物的相关分析

Analysis of microRNA-122 as a biomarker for early evaluation of drug hepatotoxicity

目的:探讨micro RNA-122(miR-122)在新药肝细胞毒性早期评价中的应用价值。方法:建立对乙酰氨基酚诱导的小鼠原代肝脏细胞损伤模型,对细胞培养上清中miR-122含量以及传统细胞毒性标志物乳酸脱氢酶(lactic dehydrogenase,LDH)含量分别进行测定,对二者进行平行比对和相关性分析,初步探讨miR-122在新药肝细胞毒性早期评价中的作用;采用多种潜在肝脏毒性物质诱发的小鼠原代肝脏细胞损伤模型,进一步验证miR-122在肝细胞毒性早期评价中的应用价值。结果:在对肝细胞毒性早期评价中,miR-122和LDH呈现良好相关性(r>0.9);与LDH相比,miR-122具有更高的灵敏性。结论:miR-122作为新药肝细胞毒性早期评价标志物具有潜在应用价值。

Objective：To investigate the value of micro RNA-122（miR-122）in the evaluation of hepatotoxicity at the early stage.Methods：Based on mouse primary liver cell injury models induced by acetaminophen,the concentrations of miR-122 and traditional cytotoxic marker lactic acid dehydrogenase（LDH）in the cell culture supernatant were measured parallelly,and followed by the correlation analysis. Besides,multiple cellular models induced by different potential hepatotoxic substances were established,and the concentrations of miR-122 and LDH in supernatant were analyzed and compared. The advantage of miR-122 for hepatotoxicity evaluation was further verified. Results：There were well correlations between miR-122 and LDH for hepatotoxicity evaluation（r 0.9）;Moreover,miR-122 demonstrated higher sensitivity compared with LDH. Conclusion：miR-122 has potential application value as a biomarker for early evaluation of drug hepatotoxicity.