emamectin苯甲酸酯在农业生产中的存在频率凸显了研究其对人类肠上皮屏障(IEB)的毒性的必要性。在这里,我们将Caco-2细胞模型与转录组分析相结合,以评估甲氨基阿维菌素苯甲酸盐的肠道毒性及其致病潜力.结果表明,甲氨基阿维菌素苯甲酸盐在暴露24、48和72h后对Caco-2细胞活力的半数最大抑制浓度(IC50)分别为18.1、9.9和8.3μM。分别。甲氨基阿维菌素苯甲酸盐暴露增强了Caco-2单层细胞旁通透性,损坏了IEB,细胞凋亡增加。42例凋亡相关DEGs的关键驱动基因分析,鉴定出10个基因(XIAP,KRAS,MCL1,NRAS,PIK3CA,CYCS,MAPK8,CASP3,FADD,和TNFRSF10B)与甲氨基阿维菌素苯甲酸盐诱导的细胞凋亡相关性最强。转录组学鉴定出326个差异表达基因(DEGs,204上调,122下调)。神经变性的功能术语-多种疾病被最多的DEG丰富,帕金森病途径的富集程度最高。我们的发现为emamectin苯甲酸酯的环境毒理学研究和健康风险评估提供了支持。
The frequency presence of emamectin benzoate in agricultural production highlights the need for studying their toxicity against human intestinal epithelial barrier (IEB). Herein, we combined a Caco-2 cell model with transcriptome analysis to assess the intestinal toxicity of emamectin benzoate and its disease-causing potential. Results showed that the half maximal inhibitory concentration (IC50) of emamectin benzoate on Caco-2 cell viability after 24, 48, and 72 h of exposure were 18.1, 9.9, and 8.3 μM, respectively. Emamectin benzoate exposure enhanced the Caco-2 monolayer paracellular permeability, damaged the IEB, and increased cellular apoptosis. Key driver gene analysis of 42 apoptosis - related DEGs, identified 10 genes (XIAP, KRAS, MCL1, NRAS, PIK3CA, CYCS, MAPK8, CASP3, FADD, and TNFRSF10B) with the strongest correlation with emamectin benzoate - induced apoptosis. Transcriptomics identified 326 differentially expressed genes (DEGs, 204 upregulated and 122 downregulated). The functional terms of neurodegeneration - multiple diseases was enriched with the most number of DEGs, and the Parkinson disease pathway had the highest enrichment degree. Our findings provided support for environmental toxicology studies and the health risk assessment of emamectin benzoate.