论文部分内容阅读
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(P<0.05),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(P<0.01)。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。
Objective To investigate the effects of neutrophil gelatinase-associated lipocalin (NGAL), renal injury factor 1 (KIM-1) and interleukin 18 (IL-18) Changes in Injury and Their Significance in Combination Detection. Methods Twelve Wistar rats were randomly divided into two groups: 12 cases of aristolochic acid (25 mg · kg -1) and 12 of control group (equal volume of normal saline). Blood and urine samples were taken at different time points and were dissected in batches one week after the last administration and withdrawal. Biochemical analyzer was used to detect the contents of serum urea nitrogen (BUN) and creatinine (Cr), and the urine concentrations of NGAL, KIM-1 and IL-18 were detected by enzyme linked immunosorbent assay (ELISA) The morphological changes of renal pathological tissues were observed under light microscope. ROC curves were used to compare the curve area of each serum or urine marker and its combination. Results Compared with the control group, the serum levels of BUN and Cr in the aristolochic group were significantly increased after the last administration (P <0.05), and recovered after one week of withdrawal , Urinary NGAL, KIM-1 and IL-18 were significantly increased at different time points (P <0.01). ROC analysis showed that the combined assay could improve the performance. The area under the curve of NGAL + KIM-1 and NGAL + KIM-1 + IL-18 combinations were 0.928 and 0.927, respectively, much higher than that of BUN and Cr and their combination BUN + Cr. Conclusion The combination of urinary NGAL, KIM-1 and IL-18 can improve the test efficiency and predict or prompt the renal tubule injury induced by aristolochic acid.