目的：观察高同型半胱氨酸（HCY）对大鼠海马基因表达谱的影响。方法：10只雄性SD大鼠随机分为 对照组和高HCY组。高HCY组大鼠皮下注射L-HCY（60 μg/g），2次/日，连续注射14 d；对照组注射等量生 理盐水。造模完成后取血浆分析HCY水平；提取海马组织RNA采用BGISEQ-500技术进行测序。测序数 据通过主成分分析进行样本间的比较，找出并剔除离群样品，DEGseq方法分析组间差异表达基因。根据 KEGG注释结果以及官方分类，将差异基因进行生物通路分类和富集分析。结果：高HCY组大鼠血HCY明 显高于对照组（P＜0.01）。大鼠海马 RNA 测序数据使用 DEGseq 总共筛选到 34 个有显著性差异表达的 mRNA，生物通路分类和富集分析找到最主要的通路是神经活动配体-受体相互作用通路。结论：高HCY血 症导致大鼠海马的基因表达谱改变，影响神经活动配体-受体相互作用等生物通路。

To observe the effect of homocysteine (HCY) on the gene expression profile in rat hippocampus. Methods: Ten male SD rats were randomly divided into the control group and the high HCY group. For 14 consecutive days, high HCY group rats were injected subcutaneously with L-HCY at 60 μg/g twice a day, and control group rats were injected with equal doses of saline. The plasma HCY of each group was analyzed after establishment of model; hippocampus RNA was extracted, and sequencing was completed via BGISEQ-500 sequencing. Principal component analysis was used to compare the samples and exclude the outliers. The differentially expressed genes (DEGs) between groups were analyzed by DEGseq. According to the annotation results of KEGG and official categories, biological pathway classification and enrichment analysis were conducted on the DEGs. Results: The plasma HCY level of the high HCY group was significantly higher than that of the control group (P＜0.01). A total of 34 mRNA with significant difference in expression were screened from rat hippocampus RNA sequencing data using DEGseq. The major pathway found by biological pathway classification and enrichment analysis was the neuroactive ligand-receptor interaction pathway. Conclusion: Hyperhomocysteinemia leads to changes in the gene expression profile of rat hippocampus and interferes with the neuroactive ligand-receptor interaction and other biological pathways.