基于HK-2细胞评价药物肾毒性生物标志物的研究

Research on the Drug Renal Toxicity Biomarkers Based on HK-2 Cells

目的筛选对药物引起的肾毒性较为灵敏的标志物进行预测与分析,加速药物早期研发。方法以人肾皮质近曲小管上皮细胞(HK-2)为研究对象,利用3种肾毒性药物(顺铂、庆大霉素和马兜铃酸I),筛选高灵敏度的生物标志物。结果生物标志物在细胞内液的灵敏度高于细胞外液;与检测单一的生物标志物相比,细胞内液中β2-微球蛋白(β2-MG)和中性粒细胞明胶酶相关载脂蛋白(NGAL)的联合检测提高肾毒性评价的准确性。结论基于HK-2细胞模型,联合检测细胞内液中β2-MG和NGAL的含量可用于药物早期开发阶段预测肾毒性。

Objective Screening for sensitive biomarkers for predicting and analyzing drug-induced renal toxicity,accelerates drug early development.Methods Focuses on epithelial cells of proximal convoluted tubules in human renal cortex(human kidney-2,HK-2)cells as the research object,screening for highly sensitive biomarkers using three nephrotoxic drugs(cisplatin,gentamicin,and aristolochic acid I).Results The sensitivity of biomarkers in intracellular fluid is higher than in extracellular fluid,compared to detecting a single biomarker in the intracellular fluid.The combined detection ofβ2-microglobulin(β2-MG)and neutrophil gelatinase-associated lipocalin(NGAL)improved the accuracy of renal toxicity evaluation.Conclusion Based on the HK-2 cell model,the combined detection ofβ2-MG and NGAL in intracellular fluid can be used to predict renal toxicity in the drug’s early development stage.