中国药理学与毒理学杂志2017，Vol.31Issue(7)：714-721,8.DOI:10.3867/j.issn.1000-3002.2017.07.003
血清miR-122作为药物肝损伤生物标志物的敏感性和特异性比较
Comparison on sensitivity and specificity of serum miR-122 as biomarkers of drug-induced liver injury
摘要
Abstract
OBJECTIVE To make a comparison of sensitivity and specificity between serum miR-122 and traditional biomarkers of drug-induced liver injury. METHODS Acetaminophen (APAP, 1250 mg · kg-1, ig), α-naphthylisothiocyanate (ANIT, 150 mg · kg-1, ig), methionine-choline deficient diet (MCDD, free feeding) and carbon tetrachloride (CCl4, 50%, ip) were used to establish hepatocellular injury, cholestasis, steatosis and fibrosis models, respectively, which were used to evaluate the sensitivity of serum miR-122 as a biomarker of drug-induced liver injury, when compared with the traditional biomarkers. Isoprenaline hydrochloride (IH) and gentamicin (GM) were used to establish myocardial and renal injury models, respectively, which were used to evaluate the specificity of serum miR-122, when compared with the tradi-tional biomarkers. Serum and liver tissues were collected at different time points during the study. Tradi-tional biomarkers such as glutamic-pyruvic transaminase (GPT), glutamic-oxaloacetic transaminase (GOT) and total bilirubin (TBIL) were measured with an automatic biochemistry analyzer. MiR-122 was detected with real- time quantitative PCR. Histopathological examination with HE staining was performed for liver tissues. RESULTS Serum miR-122 increased significantly earlier [miR-122 was signifi-cantly increased (>2 fold) at 1.5 h, 3 h, 2 weeks and 4 weeks after treatment in the four models respec-tively, while no significant increase (<2 fold) was observed for GPT, GOT and TBIL at 6 h, 12 h, 3 weeks and 6 weeks after treatment in the four models respectively] and more signficantly (the maximum fold change for miR-122 was 235.8, 202.7, 73.8 and 600.3 for the four models, respectively. For the GPT, the maximum fold change was 9.5, 3.9, 2.5 and 6.6, respectively; 6.0, 2.4, 1.4 and 3.5 respectively for GOT; 2.6, 2.3, 1.2 and 1.8 respectively for TBIL) than that of traditional biomarkers in hepatocellular injury, cholestasis, steatosis and fibrosis models, when compared with the control group. In the myocar-dial injury model, a significant increase of GOT was observed after IH treatment (2.1 fold), while no change was observed for serum miR-122. In the renal injury model, no false positive results were observed for serum miR-122. CONCLUSION Serum miR-122 can be used as a biomarker of drug-induced liver injury and serum miR-122 is more sensitive and specific than traditional biomarkers (such as GPT, GOT and TBIL).关键词
肝损伤/生物标志物/miR-122/敏感性/特异性Key words
liver injury/biomarkers/miR-122/sensitivity/specificity分类
医药卫生引用本文复制引用
汤纳平,陈洁,王雁,葛帅,马璟,梅其炳..血清miR-122作为药物肝损伤生物标志物的敏感性和特异性比较[J].中国药理学与毒理学杂志,2017,31(7):714-721,8.基金项目
国家自然科学基金(81273603) （81273603）
上海市青年科技启明星计划(14QB1400400) （14QB1400400）
上海科委实验动物专项基金(14140900900) The project supported by National Natural Science Foundation of China (81273603) （14140900900）
Shanghai Rising-Star Program (14QB1400400) （14QB1400400）
and Specified Fund of Laboratory Animal Study of the Science and Technology Commission of Shanghai Municipality (14140900900) （14140900900）
