LncRNA expression profile and their possible regulatory role in the HSOS induced by monocrotaline in rats

Aims: Long noncoding RNA (lncRNAs) contribute in regulating vital physiological processes and pathogenesis of many diseases. Monocrotaline can cause large-scale outbreaks of toxic liver disease in humans and animals as hepatic sinusoidal obstruction syndrome (HSOS). This research aimed to study the lncRNA-mRNA regulation network in MCT-induced HSOS in rats. Main methods: We established MCT-induced HSOS, and then carried out microarray to liver tissues of SD rat of an early HSOS model (MCT-12h treated and control groups) to investigate the differentially expressed lncRNAs and mRNAs in the early hepatotoxicity, followed by RT-PCR for selected lncRNAs, which were markedly changed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome analysis were also conducted Key findings. According to analysis, LncRNAs might play an essential role in the hepatotoxicity mechanism. Significance: This study provides a basis for further researches on the molecular mechanisms, and treatment of MCT-induced hepatotoxicity, especially in the early stage, which is pivotal to treat it successfully before irreversible liver damage occur.研究目的：长链非编码RNA（long noncoding RNA，lncRNA）参与调控多种重要生理过程以及诸多疾病的发病机制。野百合碱（Monocrotaline，MCT）可在人类与动物中引发大规模中毒性肝病暴发，即肝窦阻塞综合征（hepatic sinusoidal obstruction syndrome，HSOS）。本研究旨在探究大鼠野百合碱诱导的肝窦阻塞综合征模型中lncRNA与mRNA的调控网络。 主要方法：本研究先构建野百合碱诱导的肝窦阻塞综合征大鼠模型，选取早期肝窦阻塞综合征模型（经12h野百合碱处理组与对照组）的肝脏组织进行基因芯片检测，以探究早期肝毒性过程中差异表达的lncRNA与mRNA；随后对筛选出的差异显著的lncRNA进行逆转录聚合酶链反应（RT-PCR）验证。同时开展基因本体（Gene Ontology，GO）功能富集分析与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析。 核心研究结果：经分析可知，lncRNA可能在肝毒性的发病机制中发挥关键作用。 研究意义：本研究为后续深入探究野百合碱诱导的肝损伤的分子机制与治疗方案提供了理论基础，尤其是针对疾病早期阶段——该阶段是在不可逆肝损伤发生前成功实现干预的关键窗口期。