尿基质金属酶蛋白抑制剂-2和胰岛素样生长因子结合蛋白7联合检测在对比剂诱导急性肾损伤中的早期预测作用  

Predictive values of urinary metalloproteinases-2 and insulin-like growth factor-binding protein 7 for contrast medium-induced acute kidney injury

作　　者：邹晓彪 包维为 黄晓莹 卢晨 陈娟 王志清 黄明方 Zou Xiao-biao;Bao Wei-wei;Huang Xiao-ying;Lu Chen;Chen Juan;Wang Zhi-qing;Huang Ming-fang(Department of Cardiovascular Medicine,Linquan People's Hospital,Fuyang 236000,China;Department of Cardiovascular Medicine,No.900 Hospital,Joint Support Force,Fuzhou 350025,China;De-partment of Laboratory Medicine,No.900 Hospital,J oint Support Force,Fuzhou 350025,China)

机构地区：[1]临泉县人民医院心血管内科,阜阳236000 [2]联勤保障部队第九〇〇医院心血管内科,福州350000 [3]联勤保障部队第九〇〇医院检验科,福州350000

出　　处：《临床肾脏病杂志》2022年第3期221-227,共7页Journal Of Clinical Nephrology

摘　　要：目的 探讨对比剂(contrast medium,CM)损伤后,基质金属酶蛋白抑制剂-2(tissue inhibitor of metalloproteinases-2,TIMP-2)和胰岛素样生长因子结合蛋白7(insulin-like growth factorbinding protein 7,IGFBP7)在肾组织及尿液中的表达及尿[TIMP-2]·[IGFBP7]对急诊经皮冠状动脉介入治疗(primary percutaneous coronary intervention,PPCI)患者术后发生对比剂诱导的急性肾损伤(contrast-induced acute kidney injury,CI-AKI)的早期预测作用。方法 将20只大鼠按随机数字表法分为CI-AKI组(n=9)和对照组。采集大鼠术前及术后24 h动脉血液,检测血肌酐(serum creatinine,Scr);术后24 h采集大鼠肾组织标本,采用HE染色评价肾组织损伤情况,并于电镜下观察肾小管上皮细胞超微结构改变情况;进行免疫组化及蛋白质印迹法检测,观察TIMP-2和IGFBP7在肾组织中的表达。收集大鼠术前、术后4 h、12 h、24 h尿标本,采用酶联免疫吸附法(Enzyme linked immunosorbent assay,ELISA)方法检测尿TIMP-2和尿IGFBP7水平。临床上,纳入临泉县人民医院2019年6月至2020年12月行PPCI患者109例,收集患者的一般资料及实验室检查指标,留取术前、术后6 h、12 h、24 h尿标本,使用NephroCheck?试剂盒检测尿[TIMP-2]·[IGFBP7]水平,绘制术后6 h尿[TIMP-2]·[IGFBP7]预测CI-AKI的ROC曲线,评估其对于CI-AKI早期预测的价值。结果 CI-AKI组大鼠术后24 h的Scr升高,显著高于对照组,差异有统计学意义(P<0.05)。与对照组相比,CI-AKI组大鼠肾组织HE染色可以观察到明显的小管上皮细胞空泡样变性、核固缩及凋亡小体形成,Paller评分明显高于对照组(P<0.05),电镜下可见广泛线粒体自噬体形成。CI-AKI组大鼠术后尿TIMP-2水平于术后4 h达到峰值,显著高于同期对照组水平(P<0.05)。CI-AKI组大鼠尿IGFBP-7水平于术后4 h开始升高,12 h达峰,术后4 h及12 h水平均高于同期对照组(P<0.05)。免疫组化和蛋白质印迹法结果显示,CM损伤后,TIMP-2和IGFBP7在肾�Objective To explore the expressions of tissue inhibitor of metalloproteinases-2(TIMP-2)and insulin-like growth factor-binding protein 7(IGFBP7)in renal tissue and urine after an injury of contrast medium(CM)and the prediction values of urinary TIMP-2 and IGFBP7 for contrastinduced acute kidney injury(CI-AKI) in patients with primary percutaneous coronary intervention(PPCI). Methods Twenty male Sprague-Dawley rats were divided randomly into two groups of CIAKI(n=9)and control(n=11). Serum creatinine(Scr)level was measured before an injection of CM or normal saline(NS)and at 24h post-intervention. Kidney samples,containing both cortex and medulla,were harvested for hematoxylin-eosin(HE)staining and immunohistochemistry. Urinary samples for TIMP-2 and IGFBP7 were collected at 4/12/24 h post-injection. From January 2019 to December 2020,116 patients undergoing PPCI were recruited. Baseline profiles and laboratory findings were recorded.Receiver operating curves(ROC)of urinary TIMP-2/IGFBP7 concentrations at 6 h post-CI-AKI were evaluated for the possibility of serving as potential biomarkers in early prediction of CI-AKI. Results As compared with control group,the average elevation of Scr was over baseline in CI-AKI group(P<0. 05). CM intervention induced marked histopathological changes in kidney tissue,including vacuole-like denaturation,nucleus pyknosis and apoptotic body formation. The mean Paller score was significantly higher in CI-AKI group. A robust formation of autophagosome was observed with transmission electron microscope in CI-AKI group. Rising significantly and peaking at 4 h after CM injection,urinary levels of TIMP-2 were higher than those in controls at the same observation timepoints(P<0. 05). Urinary IGFBP7 levels were markedly up-regulated at 4 h after CM injection and peaked within 12 h. And the values were higher than those in controls at the same observation timepoints(P<0. 05). The expression of TIMP-2/IGFBP7 was significantly elevated in renal tubular epithelial cells after CM injury. CI-AKI

关 键 词：对比剂诱导急性肾损伤 基质金属酶蛋白抑制剂-2 胰岛素样生长因子结合蛋白7 

分 类 号：R692[医药卫生—泌尿科学]