CYP2E1稳定高表达肝细胞系的构建及其在药物性肝损伤活性筛选模型中的应用OACSTPCD
Liver cell line with stable expression of CYP2E1 and its application in screening hepatoprotective compounds for drug-induced liver injury
药物性肝损伤是临床常见且严重的药物不良反应之一,对乙酰氨基酚是临床常用的解热镇痛药,是引起药物性肝损伤的常见因素.肝微粒体酶细胞色素P450 2E1(CYP2E1)在对乙酰氨基酚诱导的肝细胞损伤中发挥了重要作用.由于体外培养的肝细胞系几乎不表达微粒体酶CYP2E1,采用CYP2E1-慢病毒转染人肝癌细胞系HepG2 构建了稳定高表达CYP2E1 基因的肝细胞系,利用该细胞系建立了对乙酰氨基酚诱导的肝细胞损伤体外筛选模型,并对实验室从中药香附中提取得到24 个天然产物进行了活性筛选,发现了8 个具有潜在体外抗药物性肝损伤活性的天然化合物.本研究为药物性肝损伤提供了合适的体外筛选模型,活性筛选结果也为传统中药香附的研究与开发提供了理论依据.
Drug-related liver injury is one of the most common and serious adverse drug reactions in clinic.Acet-aminophen,a commonly used clinical antipyretic and analgesic,is a common factor causing drug-related liver in-jury.The hepatic microsomal enzyme cytochrome P450 2E1(CYP2E1)plays an important role in acetaminophen-induced hepatocyte injury.Since in vitro cultured hepatocyte lines barely express microsomal enzyme CYP2E1,a hepatocyte line stably and highly expressing CYP2E1 gene were conducted using the human hepatoma cell line HepG2 transfected by CYP2E1-lentivirus,and an assay for screening inhibitors for acetaminophen-induced hep-atocyte injury was performed with this cell line.The results showed that eight natural compounds with potential in vitro activity against drug-induced liver injury were identified.This study provides a suitable in vitro screening model for drug-induced liver injury,and the results from the screening also provide a theoretical basis for the re-search and development of the traditional Chinese medicine Cyperus rotundus L..
裴少非;熊加燕;邹其虎;曾桂源;易春蝶;马骏杰;李金梅;谢冰;曾广智
云南民族大学 民族医药学院,云南 昆明,650500
药学
对乙酰氨基酚CYP2E1药物性肝损伤活性筛选天然产物
acetaminophenCYP2E1drug-induced liver injuryactivity screeningnatural products
《云南民族大学学报(自然科学版)》 2024 (005)
596-602 / 7
国家自然科学基金(31760095);云南省高校重点实验室建设计划.
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