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目的:探讨基于表达谱标签相似性比较的途径从上市药物中筛选发现抗辐射损伤治疗药物。方法:从GEO数据库获得辐射损伤基因表达谱数据集GSE26835,利用RMA和SAM软件对表达谱芯片数据进行差异表达基因分析,获得辐射损伤基因标签,最后通过connectivity map数据库进行检索,并对检索结果进行实验验证。结果:获得的辐射基因标签包含上调基因134个,下调基因73个,这些基因生理功能主要集中于DNA损伤应激,DNA修复,细胞周期阻滞等;通过Cmap分析,筛选到阿米洛利,潘必啶等候选药物,其中阿米洛利负相关指数最高,进一步实验验证证明阿米洛利在体外和体内实验中都具有较好的抗辐射活性。结论:基于基因表达谱的药物重定位可从上市药物中筛选到有效的抗辐射药物为发现老药的新用途提供了新的途径。
OBJECTIVE: To explore ways to screen for anti-radiation injury drugs from listed drugs based on the comparison of expression label similarity. METHODS: Gene expression profile GSE26835 was obtained from the GEO database. Gene expression profiles were analyzed using RMA and SAM software to obtain gene tags of radiation damage genes. Finally, the database was searched through the connectivity map database and the results were retrieved Experimental verification. Results: The radiolabeled genes contained 134 up-regulated genes and 73 down-regulated genes. The physiological functions of these genes mainly focused on DNA damage stress, DNA repair, cell cycle arrest, etc. Through the Cmap analysis, amiloride, Panperidine waiting for drug selection, Amoxicillin negative correlation index highest, further experimental verification shows that Amiloride in vitro and in vivo experiments have good anti-radiation activity. CONCLUSIONS: Drug relocation based on gene expression profiling can screen effective anti-radiation drugs from listed drugs and provide new avenues for finding new uses of old drugs.