Yang Rui, Bai Qingyun, Zhang Jiaqi, Sheng Yuchen, Ji Lili
1 Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
2 Shanghai Key Laboratory of Complex Prescription, MOE Key Laboratory for Standardization of Chinese Medicines, SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Hum Exp Toxicol. 2017 Aug;36(8):823-832. doi: 10.1177/0960327116666651. Epub 2016 Sep 7.
MicroRNA (miRNA) has been reported to play important roles in regulating drug-induced liver injury. Ethyl acetate extract isolated from rhizoma Dioscoreae bulbifera (EF) has been reported to induce hepatotoxicity in our previous studies. This study aims to observe the altered liver miRNA profile and its related signalling pathway involved in EF-induced hepatotoxicity. Serum alanine/aspartate aminotransferase assay showed that EF (450 mg/kg)-induced hepatotoxicity in mice. Results of miRNA chip analysis showed that the expression of eight miRNAs was up-regulated and of other nine miRNAs was down-regulated in livers from EF-treated mice. Further, the altered expression of miR-200a-3p, miR-5132-5p and miR-5130 was validated using real-time polymerase chain reaction (PCR) assay. There were total seven predicted target genes of miR-200a-3p, miR-5132-5p and miR-5130. Only one kyoto encyclopedia genes and genomes pathway was annotated using those target genes, which is protein processing in endoplasmic reticulum (ER). Furthermore, liver expression of DnaJ subfamily A member 1, a key gene involved in protein processing in ER based on the altered miRNAs, was increased in EF-treated mice. In conclusion, the results demonstrated that EF altered the expression of liver miRNA profile and its related signalling pathway, which may be involved in EF-induced hepatotoxicity.
据报道，微小RNA（miRNA）在调节药物性肝损伤中发挥重要作用。在我们之前的研究中，已报道从黄独根茎中分离出的乙酸乙酯提取物（EF）可诱导肝毒性。本研究旨在观察EF诱导肝毒性过程中肝脏miRNA谱的变化及其相关信号通路。血清丙氨酸/天冬氨酸转氨酶检测显示，EF（450mg/kg）可诱导小鼠肝毒性。miRNA芯片分析结果显示，在EF处理的小鼠肝脏中，8种miRNA的表达上调，另外9种miRNA的表达下调。此外，使用实时聚合酶链反应（PCR）检测验证了miR-200a-3p、miR-5132-5p和miR-5130表达的改变。miR-200a-3p、miR-5132-5p和miR-5130共有7个预测靶基因。使用这些靶基因仅注释了一个京都基因与基因组百科全书通路，即内质网（ER）中的蛋白质加工。此外，基于miRNA的改变，内质网中参与蛋白质加工的关键基因DnaJ亚家族A成员1在EF处理的小鼠肝脏中的表达增加。总之，结果表明EF改变了肝脏miRNA谱及其相关信号通路的表达，这可能与EF诱导的肝毒性有关。
