运动改善小鼠非酒精性脂肪肝纤维化的生物信息学分析

关键词：肝纤维化  运动  康复  高强度间歇运动  生物信息学

Keywords:liver fibrosis  exercise  rehabilitation  high-intensity intermittent exercise  bioinformatics

摘要：

      摘要 目的：肝纤维化通常是慢性肝病损伤的结果，有可能发展为肝硬化和肝癌。运动可改善肝纤维化的进程，但其相关机制仍不明确。本研究结合转录组学、基因本体论（GO）、京都基因百科全书（KEGG）分析和Cytoscape等生物信息学技术，筛选了运动调控肝纤维化过程中的关键基因和相关通路。 方法：通过对高脂喂养的非酒精性脂肪性肝病（NAFLD）小鼠模型的肝脏进行转录组测序，选取模型组与不同运动组（有氧运动组和高强度间歇运动组）的差异基因取交集，筛选条件为：qValue<0.05，|FoldChange|>2，确定显著差异表达基因（DEGs），以进一步确定运动调控纤维化的hub基因与关键富集通路。 结果：与模型组相比，有氧运动组（A组）有144个上调基因，930个下调基因；高强度间歇运动组（H组）有122个上调基因，559个下调基因以及23个Hub基因。GO和KEGG结果表明，DEGs富集的功能和途径包括细胞黏附、胶原纤维组织、蛋白质结合、ECM受体相互作用、PI3K/AKT信号通路等，并筛选出23个关键基因。 结论：运动可促进非酒精性脂肪肝相关肝纤维化的康复，通过生物信息学筛选出关键通路及Hub基因，有望成为运动相关非药物干预肝纤维化康复策略中生物标志物。

Abstract:

      Abstract Objective： Hepatic fibrosis is usually the result of chronic liver disease damage， which may develop into cirrhosis and liver cancer. Exercise can improve the progression of liver fibrosis， but its related mechanisms are still unclear. This study combined transcriptome， gene ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis， Cytoscape， and other bioinformatics technologies to screen key genes and related pathways in the exercise intervention regulating liver fibrosis. Method： The liver of nonalcoholic fatty liver disease （NAFLD） mice fed a high-fat diet was sequenced by transcriptome， and the differentially expressed genes （DEGs） between the model group and different exercise groups （aerobic exercise group and high-intensity intermittent exercise group） were selected for intersection. The screening conditions were qValue<0.05 and |FoldChange|>2， and the differentially expressed genes （DEGs） were determined. To further determine the hub genes and key enrichment pathways involved in motor regulation of fibrosis. Result： Compared with the model group， the aerobic exercise group （Group A） had 144 upregulated genes and 930 downregulated genes. The high-intensity intermittent exercise group （H group） had 122 upregulated genes， 559 downregulated genes， and 23 Hub genes. GO and KEGG results showed that the functions and pathways of DEG enrichment included cell adhesion， collagen fiber tissue， protein binding， ECM receptor interaction， and the PI3K/Akt signaling pathway， and 23 key genes were screened. Conclusion： Exercise can promote the rehabilitation of nonalcoholic fatty liver-related liver fibrosis. The key pathway and Hub genes are screened through bioinformatics， which is expected to be biomarkers in exercise-related nondrug rehabilitation strategies for liver fibrosis.