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目的:研究抗结核药物肝毒性(anti-tuberculosis drug-induced hepatotoxicity,ATDH)与非ATDH患者化疗前血浆差异性表达的miRNA分子,为ATDH易感者筛检提供新的生物学指标.方法:采用miRNA芯片检测ATDH及对照患者化疗前血浆标本.对存在差异表达趋势的25种miRNA分子,采用高通量实时荧光定量PCR进行分析验证.应用互联网上miRNA靶基因预测软件对表达上调的miRNA进行靶基因预测,并采用PANTHER tool查找靶蛋白GO功能分类.结果:与对照组相比,ATDH患者化疗前血浆中共检出7个差异性表达的miRNA分子,其中表达上调的miRNA有4个,包括miR-4284、miR-3620、miR-652-5p和miR-4800-5p;表达下调的miRNA有3个,包括miR-338-3p、miR-424-5p和miR-194-5p.结论:ATDH患者化疗前血浆内存在差异性表达的miRNA分子,其中表达上调的miRNA分子(特别是miR-4284)可能作为ATDH易感者筛检的生物学指标.
Objective: To study the miRNAs differentially expressed in plasma before chemotherapy in patients with anti-tuberculosis drug-induced hepatotoxicity (ATDH) and non-ATDH, and to provide new biological indicators for the screening of ATDH susceptibles.Methods: miRNA microarray was used to detect plasma samples from patients with ATDH and control before chemotherapy, and 25 miRNAs with different expression trend were analyzed and confirmed by high-throughput real-time fluorescence quantitative PCR.The miRNA target genes prediction software Gene prediction, and the use of PANTHER tool to find the target protein GO functional classification.Results: Compared with the control group, a total of 7 differentially expressed miRNA molecules were detected in plasma of patients with ATDH before chemotherapy, including 4 miRNAs that were up-regulated, including miR -4284, miR-3620, miR-652-5p and miR-4800-5p, and there were three miRNAs downregulated including miR-338-3p, miR-424-5p and miR-194-5p.Conclusions: There are differentially expressed miRNA molecules in plasma before chemotherapy, in which miRNAs (especially miR-4284) whose expression is upregulated may be used as biological markers for the screening of susceptible people with ATDH.