目的 探讨利用高内涵分析技术对药物进行肾毒性筛选的可行性。方法 选择罗格列酮(rosiglitazone)为阴性药,缬氨霉素(valinomycin)为阳性药,利用高内涵分析技术,通过检测细胞数目(cell number)、DNA含量(DNA intensity)、细胞膜通透性(cell permeability)、线粒体膜电位(mitochondrial membrane potential,MMP)、细胞色素C(cytochrome C)的释放这5个指标,建立高内涵HK-2肾细胞毒性筛选模型并利用具有明显肾毒性的药物马兜铃酸A(aristolochic acid A)和顺铂(cisplatin)对该模型进行验证。结果 缬氨霉素、顺铂和马兜铃酸A可以检测到明确的HK-2肾细胞毒性,而罗格列酮即使在药物浓度为最大血药浓度的1 000倍情况下仍然不会检测到明显的HK-2肾细胞毒性。结论 基于HK-2肾细胞,高内涵平台可以用于对药物进行肾细胞毒性筛选。
Abstract
OBJECTIVE To discuss the feasibility of renal toxicity screening of drugs using high content analysis technology.METHODS Rosiglitazone was selected as the negative drug and valinomycin was selected as the positive drug. High intension HK-2 renal cell toxicity screening model was established through testing five indexes including cell number, DNA intensity, cell permeability, mitochondrial membrane potential and cytochrome C, using high content analysis technology. Aristolochic acid A and cisplatine that has obvious renal toxicity was used to validate the model. RESULTS Valinomycin, cisplatin and aristolochic acid A has obvious renal toxicity;rosiglitazone don′t have renal toxicity. CONCLUSION High content analysis can be used to screen renal toxicity of drugs.
关键词
高内涵分析技术 /
肾毒性 /
毒性筛选
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Key words
high content analysis /
nephrotoxicity /
renal toxicity screening
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中图分类号:
R965
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参考文献
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脚注
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