长期低氧对斑马鱼肝脏糖脂代谢的影响  

Effects of long-term hypoxia acclimation on liver glycolipid metabolism in zebrafish(Danio rerio)

作　　者：王彦欣 向蒙 陈磊 咸晨微[1,2] 胡瑞芹 周艳 许强华 WANG Yanxin;XIANG Meng;CHEN Lei;XIAN Chenwei;HU Ruiqin;ZHOU Yan;XU Qianghua(College of Marine Sciences,Shanghai Ocean University,Shanghai 201306,China;Key Laboratory of Sustainable Exploitation of Ocean Fisheries Resources,Ministry of Education,Shanghai 201306,China;International Research Center for Marine Biosciences,Ministry of Science and Technology,Shanghai 201306,China;Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources,Ministry of Education,Shanghai 201306,China)

机构地区：[1]上海海洋大学海洋科学学院,上海201306 [2]大洋渔业资源可持续开发教育部重点实验室,上海201306 [3]国家海洋生物科学国际联合研究中心,上海201306 [4]水产种质资源发掘与利用教育部重点实验室,上海201306

出　　处：《大连海洋大学学报》2023年第3期429-437,共9页Journal of Dalian Ocean University

基　　金：国家重点研发计划项目(2022YFD2400800);国家自然科学基金(31772826,31572598)。

摘　　要：为了解长期低氧对斑马鱼(Danio rerio)肝脏糖脂代谢方面产生的影响,采用显微观察和转录组(RNA-Seq)测序技术,比较了常氧(6.5 mg/L±0.2 mg/L)与长期低氧胁迫(1.5 mg/L±0.2 mg/L)下,斑马鱼肝脏组织的显微与超显微结构及转录组变化。结果表明:光镜及电镜切片下,长期低氧使斑马鱼肝脏细胞呈现明显空泡化、脂质堆积、线粒体膨胀及内部结构紊乱等非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的病理现象;常氧组和长期低氧组肝脏的转录组比较显示,共筛选出362个显著差异表达基因(DEGs);GO和KEGG富集分析显示,显著差异表达基因富集在碳代谢、脂质代谢和PML(promyelocytic leukemia protein)小体等信号通路或类别;相关性分析发现,富集于PML小体的基因与碳代谢、脂肪酸代谢相关基因普遍呈正相关性,推测PML小体可能作为一种保护机制起到降低长期低氧对肝脏损伤的作用。研究表明,长期低氧会造成斑马鱼肝脏糖脂代谢异常,并诱发肝细胞出现NAFLD的病理现象。To better understanding the effects of long-term hypoxia on hepatic glycolipid metabolism of zebrafish(Danio rerio),changes in the microscopic and ultramicroscopic structure changes and transcriptome were compared between the zebrafish exposed to normoxia(6.5 mg/L±0.2 mg/L)and long-term hypoxia(1.5 mg/L±0.2 mg/L).It was found that non-alcoholic fatty liver disease(NAFLD)pathological phenomena were observed in the fish exposed to long-term hypoxia,including distinct vacuolization,lipid accumulations,mitochondrial swelling,and internal structural disorders in hepatocytes under light and electron microscopic sections.Comparative transcriptomes of normoxic and hypoxic livers revealed that 362 differentially expressed genes(DEGs)were identified.GO(gene ontology)and KEGG(kyoto encyclopedia of genes and genomes)enrichment analysis showed that carbon metabolism,lipid metabolism and PML(promyelocytic leukemia protein)body were significantly enriched among the significant differentially expressed genes.Further correlation analysis revealed that genes enriched in PML body GO term were generally positively correlated with the genes involved in carbon metabolism and fatty acid metabolism pathways,indicating that PML body may act as a protective mechanism to reduce the liver damage caused by longterm hypoxia stress.The findings showed that long-term hypoxia caused abnormal liver glycolipid metabolism and induced the pathology of NAFLD in hepatocytes in zebrafish.

关 键 词：斑马鱼 长期低氧 转录组 非酒精性脂肪性肝病 糖脂代谢 

分 类 号：S917.4[农业科学—水产科学] Q71[生物学—分子生物学]