摘要
抗结核药物异烟肼具有肝脏毒性,其发生机制需要进一步阐明。本研究使用异烟肼处理肝细胞,分析不同处理时间表达谱的差异。通过对差异表达基因进行聚类分析和功能富集分析,共得到6个与肝脏毒性相关的基因簇和一系列相关通路;进一步通过蛋白互作分析和时间序列差异分析方法,筛选出表达水平具有时间依赖性的13个关键基因。本研究结果为理解异烟肼引发肝脏毒性过程提供了思路,为今后药物性肝脏毒性的监测以及治疗提供了新的靶基因。
Isoniazid(INH)is a first-line anti-tuberculosis drug which can cause idiosyncratic liver injury,while the underlying mechanisms need to be further elucidated.In this study,we explored the time series gene expression profiling of a hepatocyte cell line under isoniazid treatment.Through cluster analysis and enrichment analysis of differentially expressed genes,we revealed a total of 6 gene clusters and a series of pathways related to hepatotoxicity,and 13 key candidate genes were identified according to the protein-protein interaction(PPI)network analysis and maSigPro analysis.These findings lay a foundation for understanding the mechanisms of isoniazid-induced liver toxicity and provide new target genes for the monitoring and treatment of INH-induced hepatotoxicity in the future.
作者
田子钊
周晨希
周伟
李沫
褚云鹏
怀聪
秦胜营
Zizhao Tian;Chenxi Zhou;Wei Zhou;Mo Li;Yunpeng Chu;Cong Huai;Shengying Qin(Bio-X Institute,Shanghai Jiaotong University,Shanghai 200030,China)
出处
《遗传》
CAS
CSCD
北大核心
2022年第6期501-509,共9页
Hereditas（Beijing)
基金
国家自然科学基金项目(编号:81773818,82003856)资助。
关键词
异烟肼
肝细胞
肝脏毒性
时间序列分析
isoniazid
hepatocytes
liver toxicity
time series analysis
