多黏菌素E对肾小管上皮细胞的体外毒性研究  

Research on colistin-induced toxicity to renal tubular epithelial cells

作　　者：杨天立 王向东[2,3] 王瑾[1] 王睿[1] 蔡芸[1] YANG Tian-li;WANG Xiang-dong;WANG Jin;WANG Rui;CAI Yun(Medical Supplies Center,Department of Pharmacy,Medicine Clinical Research Center,Chinese People‘s Liberation Army General Hospital,Beijing 100853,China;Graduate School,Chinese People‘s Liberation Army General Hospital,Beijing 100853,China;Second Medical Center,Department of Hematology,Chinese People‘s Liberation Army General Hospital,Beijing 100853,China)

机构地区：[1]解放军总医院,医疗保障中心药剂科药物临床研究室,北京100853 [2]解放军总医院,研究生院,北京100853 [3]解放军总医院,第二医学中心血液科,北京100853

出　　处：《中国临床药理学杂志》2021年第24期3363-3366,3370,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81770004、82073894);解放军总医院杰青培育基金资助项目(2020-JQPY-004)。

摘　　要：目的探讨硫酸多黏菌素E (CST)和多黏菌素E甲磺酸钠(CMS)对肾小管上皮细胞的毒性。方法以大鼠肾小管上皮细胞(NRK-52E)和人肾小管上皮细胞(HK-2)为研究对象,分为CST不同浓度作用组和CMS不同浓度作用组,各组细胞与药物作用12,24和48 h,用细胞增殖与毒性检测试剂盒(CCK-8)法检测细胞存活率,用线性回归的方法计算药物对细胞的半数致死剂量。结果 10μg·mL^(-1)CST组和10μg·mL^(-1)CMS组在48 h时NRK-52E细胞的存活率分别为(99.00±3.99)%和(92.30±12.29)%;10μg·mL^(-1)CST组与10μg·mL^(-1)CMS组相比存活率高,差异均有统计学意义(均P<0.05)。1750μg·mL^(-1)CST组、2000μg·mL^(-1)CST组和2500μg·mL^(-1)CST组在24 h时HK-2细胞的存活率分别为(64.28±14.94)%,(41.59±4.72)%,(13.77±3.14)%;1750μg·mL^(-1)CST组与2000μg·mL^(-1)CST组和2500μg·mL^(-1)CST组相比存活率高,差异均有统计学意义(均P<0.05)。结论 CMS和CST对肾小管上皮细胞增殖的抑制作用与药物浓度和作用时间相关。Objective To investigate the toxicity of colistin sulfate(CST) and colistimethate sodium(CMS) to renal tubular epithelial cells. Methods Rat renal tubular epithelial cells(NRK-52 E) and human renal tubular epithelial cells(HK-2) were treated with series concentrations of CST and CMS for 12, 24 and 48 h, respectively. The cell viability was measured by cell counting kit-8(CCK-8) method, and the median lethal dose of the drug was calculated by linear regression method. Results The cell viability of NRK-52 E cells in the CST 10 μg·mL^(-1) group and CMS 10 μg·mL^(-1) group at 48 h was(99.00±3.99)% and(92.30±12.29)%;the cell viability of CST 10 μg·mL^(-1)group was higher than that of CMS 10 μg·mL^(-1) group with statistical significance(all P<0.05). The cell viability of HK-2 cells in the CST 1750 μg·mL^(-1) group, CST 2000 μg·mL^(-1) group and CST 2500 μg·mL^(-1) group at 24 h was(64.28±14.94)%,(41.59±4.72) and(13.77±3.14)%, respectively;the cell viability of CST 1750 μg·mL^(-1) group was higher than that of CST 2000 μg·mL^(-1) group and CST 2500 μg·mL^(-1) group with statistical significance(all P<0.05). Conclusion The inhibitory effects of CMS and CST on the proliferation of renal tubular epithelial cells were related to the concentration and duration of the drugs.

关 键 词：多黏菌素E 肾毒性 体外实验 半数致死剂量 

分 类 号：R97[医药卫生—药品]