探讨有参转录组测序法分析急性敌草快中毒小鼠中脑组织中基因表达谱的变化及其毒理机制。

将8只C57BL/6小鼠分成实验组及对照组，每组各4只。实验组小鼠给予300 mg/kg敌草快经口灌胃，对照组予同体积等渗NaCl溶液。染毒后第24小时，分离小鼠中脑组织并提取RNA进行有参转录组测序。通过DESeq2软件包筛选差异表达基因（DEGs），采用京都基因与基因组百科全书（KEGG）信号通路及蛋白质相互作用（PPI）网络为潜在的候选基因提供功能注释。

上调基因富集在细胞凋亡通路、肿瘤坏死因子（TNF）信号通路及缺氧诱导因子1信号通路等；而下调基因富集在神经信号调控通路与多种物质合成代谢通路，涉及神经活性配体-受体相互作用、γ-氨基丁酸能突触、细胞黏附分子以及脂质、聚糖生物合成过程。PPI网络分析显示，TNF、细胞间黏附分子1（ICAM1）、C-C基序趋化因子配体2（CCL2）、C-X-C基序趋化因子配体10（CXCL10）、核孔蛋白214（NUP214）、CCL3、血管内皮生长因子A（VEGFA）、肿瘤坏死因子受体超家族成员1A（TNFRSF1A）、血小板内皮细胞黏附分子1（PECAM1）、输出蛋白1（XPO1）为网络关键枢纽基因。

急性敌草快中毒小鼠中脑组织存在合成代谢广泛抑制与炎症/凋亡通路协同激活的转录组失衡特征。鉴定出10个关键枢纽基因，为阐明其中枢神经毒性的网络化机制及筛选干预靶点提供了分子依据。

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.