人肾小管上皮细胞及正常肝细胞在药物毒性器官选择中的应用  

Application study of the organ specific drug toxicity evaluated by human renal tubular epithelial cell line and human liver cell line cells

作　　者：王磊[1] 刘艳菊[1] 葛鹏[1] 张金晓[1] 申秀萍[1] 

机构地区：[1]天津药物研究院天津市新药安全评价研究中心,天津300301

出　　处：《中国临床药理学杂志》2015年第1期48-51,55,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家重大新药创制科技重大专项“十二五”计划基金资助项目(2012ZX09505001-001)

摘　　要：目的探讨人肾小管上皮细胞(HK-2)及人正常肝细胞(L-02)在药物毒性器官选择中的应用。方法以肾毒性药物庆大霉素、顺铂、环孢素A及肝毒性药物硫唑嘌呤作用于HK-2及L-02细胞24 h,考察并比较药物对2种细胞的形态、存活、凋亡及酶学指标变化的影响。结果肾毒性药物在较低浓度下即可引起HK-2细胞的形态、存活、凋亡及酶学指标的显著性变化,肝毒性药物则在较低浓度下即可引起L-02细胞相关指标的显著性变化;比较4种药物的IC10值发现:3种肾毒性药物对HK-2的IC10值均小于对L-02的IC10值;而肝毒性药物硫唑嘌呤的IC10值则HK-2大于L-02。结论基于HK-2及L-02细胞评价药物的毒性器官选择性是可行性的。Objective To discuss the application of the organ specific drug toxicity evaluated by human renal tubular epithelial cell line（ HK-2） and human liver cell line（ L- 02） cells.Methods HK- 2 and L-02 cells were treated with nephrotoxicity and hepatotoxic drugs included gentamicin,cisplatin,cyclosporine A and azathioprine for 24 hours to observe the changes of cell morphology,survival,apoptosis and enzymology indexes.Results The morphology,survival,apoptosis and enzymology indexes of HK- 2 cells were changed significantly at a lower concentration of nephrotoxicity drugs.And these indicators of L- 02 cells were changed significantly at a lower concentration of hepatotoxic drugs.According to the IC10 of four drugs,IC10HK- 2 was less than IC10L- 02 in three nephrotoxic drugs,and was greater than IC10L- 02 in hepatotoxic drug azathioprine.Conclusion It is feasible to evaluate the organ specific drug toxicity by HK- 2 and L- 02 cells.

关 键 词：人肾小管上皮细胞 人正常肝细胞 肾毒性 肝毒性 毒性器官选择性 

分 类 号：R969.3[医药卫生—药理学] R978.1[医药卫生—药学]