To explore the changes in gene expression profiles and their toxicological mechanisms in the midbrain tissue of mice with acute diquat poisoning analyzed by referenced transcriptome sequencing.

Eight C57BL/6 mice were divided into an experimental group and a control group, with four mice in each group. Mice in the experimental group were given 300 mg/kg diquat by oral gavage, while those in the control group were given an equal volume of isotonic NaCl solution. At 24 hours after exposure, the midbrain tissue of mice was isolated and RNA was extracted for referenced transcriptome sequencing. Differentially expressed genes were screened through the DESeq2 software package, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and protein-protein interaction (PPI) network were used to provide functional annotations for potential candidate genes.

Upregulated genes were enriched in the apoptosis pathway, tumor necrosis factor (TNF) signaling pathway, and hypoxia inducible factor-1 signaling pathway. Down-regulated genes were enriched in neural signal regulatory pathways and various synthetic metabolic pathways, involving neural active ligand-receptor interactions, γ-aminobutyric acidergic synapses, cell adhesion molecules, as well as lipid and glycan biosynthesis processes. PPI network analysis showed that TNF, intercellular adhesion molecule 1 (ICAM1), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 10 (CXCL10), nucleoporin 214 (NUP214), CCL3, vascular endothelial growth factor A (VEGFA), tumor necrosis factor receptor super family member 1A (TNFRSF1A), platelet endothelial cell adhesion molecule 1 (PECAM1), and exportin 1 (XPO1) were key hub genes in the network.

In mice with acute diquat poisoning, the midbrain tissue shows a transcriptome imbalance characterized by extensive inhibition of anabolism and coordinated activation of inflammatory/apoptotic pathways. Ten key hub genes are identified, providing a molecular basis for clarifying the networked mechanism of its central nervous system toxicity and screening intervention targets.