尿液多标志物组合检测在马兜铃酸肾毒性评价中的应用

发布时间：2018-05-31 09:44

本文选题：马兜铃酸 + 中性粒细胞明胶酶相关脂质运载蛋白　；参考：《中国新药与临床杂志》2015年07期

【摘要】：目的探讨肾损伤标志物中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤因子1(KIM-1)和白细胞介素18(IL-18)在马兜铃酸诱导的大鼠肾损伤中的变化特征及其组合检测的意义。方法取Wistar大鼠随机分为马兜铃酸(25 mg·kg-1)组和对照组(等容量生理盐水)各12只,隔两日一次尾静脉注射给药,共两周。于不同时间点采集血、尿样,于末次给药和停药一周后分批解剖处理。生化分析仪检测血清尿素氮(BUN)、肌酐(Cr)含量,酶联免疫吸附法(ELISA)检测尿液NGAL、KIM-1、IL-18浓度。光镜下观察肾脏病理组织形态学改变。采用ROC曲线比较各血清或尿液标志物及其组合的曲线面积。结果马兜铃酸组大鼠肾小管病理损伤明显,停药后亦未恢复;与对照组相比,血清BUN、Cr于末次给药后显著升高(P0.05),停药1周后均恢复,尿液NGAL、KIM-1和IL-18于不同时间点明显升高(P0.01)。ROC分析显示其组合检测可提高效能,尤其NGAL+KIM-1和NGAL+KIM-1+IL-18组合的曲线下面积分别为0.928和0.927,远高于BUN、Cr及其组合BUN+Cr。结论尿液NGAL、KIM-1和IL-18的组合检测更能提高检验效能,可预测或提示马兜铃酸诱导的肾小管损伤。
[Abstract]:Objective to investigate the changes of neutrophil gelatinase-associated lipid carrier protein (NGALL), renal injury factor (KIM-1) and interleukin-18 (IL-18) in rat kidney injury induced by aristolochic acid. Methods Wistar rats were randomly divided into two groups: control group (n = 12) and control group (n = 12). Blood and urine samples were collected at different time points. Serum bun (bun) and creatinine (Cr) were determined by biochemical analyzer, and urine NGALL KIM-1 (IL-18) was detected by enzyme linked immunosorbent assay (Elisa). The histopathological changes of kidney were observed under light microscope. The ROC curve was used to compare the area of each serum or urine marker and its combination curve. Results the pathological injury of renal tubules in aristolochic acid group was obvious and did not recover after drug withdrawal, compared with the control group, the serum bun Cr increased significantly after the last administration of aristolochic acid, and all recovered after 1 week of withdrawal. Urine NGALL KIM-1 and IL-18 increased significantly at different time points P0.01U 路ROC analysis showed that the combined detection could improve the efficiency, especially the area under the curve of the combination of NGAL KIM-1 and NGAL KIM-1 IL-18 was 0.928 and 0.927 respectively, which was much higher than that of Buchon Cr and its combination BUN Cr. Conclusion the combined detection of urinary NGALL KIM-1 and IL-18 can improve the efficiency and predict the renal tubule injury induced by aristolochic acid.
【作者单位】：上海中医药大学药物安全评价研究中心;
【基金】：国家“重大新药创制”科技重大专项项目(2009ZX09502-002) 国家重点基础研究发展计划(973计划)(2009CB522807) 上海市教委预算内项目(2010JW30)
【分类号】：R965.3

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