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利用尿液蛋白质组学对阿托伐他汀进行药 物一致性评价

Drug consistency evaluation of atorvastatin by urine proteomic

摘要:[目的] 通过尿液蛋白质组学分析对阿托伐他汀片进行药物一致性评价。 [方法] 分别建立两种药厂的阿托伐他汀片大鼠灌胃模型,收集灌胃前后的尿液,并使用液相色谱串联质谱技术(LC-MS/MS)对提取的尿蛋白进行分析,并通过DAVID数据库对差异蛋白进行生物学通路的分析。 [结果] 灌胃后和灌胃前作比较,在药物A组灌胃模型中共鉴定到116个差异蛋白,在药物B组灌胃模型中共鉴定到66个差异蛋白,其中有24个蛋白被共同鉴定到。这些差异蛋白倾向于参与细胞黏附、内肽酶活性的负调控、蛋白水解等生物学通路。 [结论] 针对产自不同药厂的阿托伐他汀片,我们可以通过尿蛋白检测到它们之间的差别,这验证了尿蛋白的灵敏性,同时提示着尿液蛋白质组学在药物一致性评价上有很大潜力。

英文摘要:[Objective] The drug consistency evaluation of atorvastatin by urine proteomic analysis. [Methods] Intragastric administration rat models were established by atorvastatin from two companies. Urine samples were collected from rats before and after intragastric administration. Urine proteins were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), and the biological pathway of the differential proteins was analyzed by DAVID database. [Results] The differential proteins were selected by comparing the after intragastric administration to before intragastric administration. A total of 116 differential proteins were identified in group A and 66 differential proteins in group B, and 24 proteins were identified in common between two groups. These differential proteins tend to be involved in biological pathways such as cell adhesion, negative regulation of endopeptidase activity and proteolysis. [Conclusions] For two kind of atorvastatin, we can detect small differences in urinary protein between them, which confirms the sensitivity of urinary protein and suggests that urine proteomics has great potential for the Drug consistency evaluation.

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[V1] 2022-03-09 10:24:29 chinaXiv:202203.00025V1 下载全文
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