目的

利用秀丽隐杆线虫（Caenorhabditis elegans）阿尔茨海默病（AD）模型，通过转录组测序分析探究其早期分子病理机制，为口腔-神经疾病研究提供实验平台。

方法

采用Illumina HiSeq平台对野生型N2和泛神经元表达人源Aβ_1-42的AD模型（CL2355）线虫进行转录组测序。通过差异表达分析、基因本体（GO）功能富集分析、京都基因与基因组百科全书（KEGG）通路分析和基因集富集分析（GSEA），系统研究基因表达谱的改变。

结果

与野生型相比，AD模型中鉴定出1 899个上调基因和2 018个下调基因。GO分析显示，上调基因显著富集于神经突起导向和细胞分化等过程，下调基因主要涉及mRNA剪接和DNA修复。KEGG分析发现，药物代谢和异物代谢通路显著上调，而RNA监控和内吞作用通路下调。GSEA 分析揭示，细胞凋亡通路显著下调（经归一化的富集分数NES=-1.775，P=0.008 1），其关键基因ced-9、ced-3等表达降低。

结论

本研究通过转录组分析揭示了AD线虫模型中基因表达的系统性变化，为探索口腔感染因素在AD发病中的作用提供了理想的实验模型。

Objective

To investigate the molecular pathological mechanisms of Alzheimer's disease（AD）through transcriptome analysis using Caenorhabditis elegans as a model organism，aiming to provide an in vivo experimental platform for oral-neural disease research.

Methods

Transcriptome sequencing was performed on wild-type N2 and AD model worms（CL2355）expressing pan-neuronal human Aβ_1-42 using Illumina HiSeq platform.Differential expression analysis，gene ontology（GO）enrichment analysis，Kyoto encyclopedia of genes and genomes（KEGG）pathway analysis，and gene set enrich analysis（GSEA）were conducted to systematically detect changes in gene expression.

Results

Compared to wild-type，1 899 upregulated and 2 018 downregulated genes were identified in the AD model. GO analysis revealed significant enrichment of upregulated genes in neurite guidance and cell differentiation，while downregulated genes were enriched in mRNA splicing and DNA repair. KEGG analysis showed significant upregulation of drug and xenobiotic metabolism pathways，and downregulation of RNA surveillance and endocytosis pathways.GSEA revealed significant downregulation of the apoptosis pathway［normalized enrichment score（NES）=-1.775，P = 0.008 1］with decreased expression of key genes including ced-9 and ced-3.

Conclusions

This study revealed systematic changes in gene expression in the C.elegans AD model，providing an ideal experimental model for investigating the role of oral infection factors in AD pathogenesis.