Comparative Transcriptome Analyses Provide Potential Insights into the Molecular Mechanisms of Astaxanthin in the Protection against Alcoholic Liver Disease in Mice
Comparative Transcriptome Analyses Provide Potential Insights into the Molecular Mechanisms of Astaxanthin in the Protection against Alcoholic Liver Disease in Mice
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比较转录组分析为虾青素预防小鼠酒精性肝病的分子机制提供了潜在的见解
DOI：
10.3390/md17030181
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发表时间：
2019-03-01
期刊：
影响因子：
5.4
通讯作者：
Fu, Xueqi
中科院分区：
文献类型：
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作者：
Liu, Huilin;Liu, Huimin;Fu, Xueqi
酒精性肝病（ALD）是世界范围内慢性肝病的主要原因。这是一个复杂的过程，包括从纤维化到肝硬化的广泛的肝脏病变。我们前期的研究表明，虾青素（AST）可以减轻乙醇引起的肝脏炎症和脂质代谢紊乱。在本研究中，将总共48只雄性C57 BL/6 J小鼠分为4组：Con组（用Lieber-DeCarli流质饮食喂养）、AST组（用Lieber-DeCarli流质饮食和AST喂养）、Et组（用含乙醇的Lieber-DeCarli流质饮食喂养）和EtAST组（用含乙醇的Lieber-DeCarli流质饮食和AST喂养）。然后，通过Illumina RNA测序进行各组之间的比较肝转录组分析。进行基因富集分析以鉴定受差异表达基因影响的途径。通过实时荧光定量PCR（qRT-PCR）和Western blot验证前几位基因的变化。Con、AST、Et和EtAST组分别获得了总计514.95 ± 6.89、546.02 ± 15.93、576.06 ± 21.01和690.85 ± 54.14百万个干净读数。与Et组相比，共检测到1892个差异表达基因（DEG），在AST组中共检测到351个上调基因和1541个下调基因，其中1724个差异表达基因，（包括233个上调和1491个下调的基因），EtAST组共检测到1718个DEG（包括1380个上调和338个下调基因）。富集分析显示，趋化因子信号，抗原加工和呈递，核苷酸结合和寡聚化结构域（NOD）样受体信号，和Toll样受体信号途径富集最差异表达的基因。这项研究的结果为ALD的营养相关疗法的发展提供了见解。
Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. It is a complex process, including a broad spectrum of hepatic lesions from fibrosis to cirrhosis. Our previous study suggested that astaxanthin (AST) could alleviate the hepatic inflammation and lipid dysmetabolism induced by ethanol administration. In this study, a total of 48 male C57BL/6J mice were divided into 4 groups: a Con group (fed with a Lieber–DeCarli liquid diet), an AST group (fed with a Lieber–DeCarli liquid diet and AST), an Et group (fed with an ethanol-containing Lieber–DeCarli liquid diet), and a EtAST group (fed with an ethanol-containing Lieber–DeCarli liquid diet and AST). Then, comparative hepatic transcriptome analysis among the groups was performed by Illumina RNA sequencing. Gene enrichment analysis was conducted to identify pathways affected by the differentially expressed genes. Changes of the top genes were verified by quantitative real-time PCR (qRT-PCR) and Western blot. A total of 514.95 ± 6.89, 546.02 ± 15.93, 576.06 ± 21.01, and 690.85 ± 54.14 million clean reads were obtained for the Con, AST, Et, and EtAST groups, respectively. Compared with the Et group, 1892 differentially expressed genes (DEGs) (including 351 upregulated and 1541 downregulated genes) were identified in the AST group, 1724 differentially expressed genes (including 233 upregulated and 1491 downregulated genes) were identified in the Con group, and 1718 DEGs (including 1380 upregulated and 338 downregulated genes) were identified in the EtAST group. The enrichment analyses revealed that the chemokine signaling, the antigen processing and presentation, the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, and the Toll-like receptor signaling pathways enriched the most differentially expressed genes. The findings of this study provide insights for the development of nutrition-related therapeutics for ALD.