Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin, China.
Key Laboratory of Cold Water Fish Germplasm Resources and Multiplication and Cultivation of Heilongjiang Province, Harbin, Heilongjiang, China.
Front Immunol. 2024 Jul 8;15:1431224. doi: 10.3389/fimmu.2024.1431224. eCollection 2024.
High-alkalinity water is a serious health hazard for fish and can cause oxidative stress and metabolic dysregulation in fish livers. However, the molecular mechanism of liver damage caused by high alkalinity in fish is unclear.
In this study, 180 carp were randomly divided into a control (C) group and a high-alkalinity (A25) group and were cultured for 56 days. High-alkalinity-induced liver injury was analysed using histopathological, whole-transcriptome, and metabolomic analyses.
Many autophagic bodies and abundant mitochondrial membrane damage were observed in the A25 group. High alkalinity decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity and the total antioxidant capacity (T-AOC) and increased the malondialdehyde (MDA) content in liver tissues, causing oxidative stress in the liver. Transcriptome analysis revealed 61 differentially expressed microRNAs (miRNAs) and 4008 differentially expressed mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that mammalian target of rapamycin (mTOR), forkhead box O (FoxO), mitogen-activated protein kinase (MAPK), and the autophagy signalling pathway were the molecular mechanisms involved. High alkalinity causes oxidative stress and autophagy and results in autophagic damage in the liver. Bioinformatic predictions indicated that Unc-51 Like Kinase 2 (ULK2) was a potential target gene for miR-140-5p, demonstrating that high alkalinity triggered autophagy through the miR-140-5p-ULK2 axis. Metabolomic analysis revealed that the concentrations of cortisol 21-sulfate and beta-aminopropionitrile were significantly increased, while those of creatine and uracil were significantly decreased.
The effects of high alkalinity on oxidative stress and autophagy injury in the liver were analysed using whole-transcriptome miRNA-mRNA networks and metabolomics approaches. Our study provides new insights into liver injury caused by highly alkaline water.
高碱性水对鱼类是一种严重的健康危害，可导致鱼类肝脏氧化应激和代谢紊乱。然而，鱼类高碱性引起肝损伤的分子机制尚不清楚。
本研究将 180 条鲤鱼随机分为对照组（C 组）和高碱性组（A25 组），培养 56 天。采用组织病理学、全转录组和代谢组学分析方法分析高碱性诱导的肝损伤。
A25 组观察到大量自噬体和丰富的线粒体膜损伤。高碱度降低了超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的活性以及总抗氧化能力（T-AOC），增加了肝组织中的丙二醛（MDA）含量，导致肝脏氧化应激。转录组分析显示 61 个差异表达 microRNAs（miRNAs）和 4008 个差异表达 mRNAs。京都基因与基因组百科全书（KEGG）富集分析显示，雷帕霉素靶蛋白（mTOR）、叉头框 O（FoxO）、丝裂原活化蛋白激酶（MAPK）和自噬信号通路是涉及的分子机制。高碱度导致氧化应激和自噬，导致肝脏自噬损伤。生物信息学预测表明，UNC-51 样激酶 2（ULK2）是 miR-140-5p 的潜在靶基因，表明高碱度通过 miR-140-5p-ULK2 轴触发自噬。代谢组学分析显示，皮质醇 21-硫酸盐和β-氨基丙腈的浓度显著增加，而肌酸和尿嘧啶的浓度显著降低。
采用全转录组 miRNA-mRNA 网络和代谢组学方法分析高碱性对肝脏氧化应激和自噬损伤的影响。本研究为高碱性水引起的肝损伤提供了新的见解。
