造影剂诱导的急性肾损伤(CI-AKI),也称为对比剂肾病(CIN),已成为医源性AKI的第三大病因。血清肌酐(Scr)目前用于CIN临床诊断。Scr升高的患者出现了严重的肾损伤,因此,迫切需要找到一种用于CIN早期诊断的生物标志物。探讨冠状动脉造影后循环微小RNA-188-5p(miR-188-5p)的变化及其对CIN发生的预测价值。分析了GEO数据库中CIN大鼠和涟水市人民医院CIN患者和对照组患者中miR-188-5p的表达。结果显示,miR-188-5p在血浆和肾脏中的表达在CIN组高于对照组。Further,共纳入36CIN患者和108例非CIN患者.年龄差异显著,高血压,糖尿病,和造影剂剂量。使用造影剂12小时后,循环miR-188-5p在CIN组的表达高于对照组。单因素和多因素logistic回归分析显示,年龄,高血压,糖尿病,造影剂用量和术后miR-188-5p表达与CIN发生密切相关。对于体外实验,ioversol处理降低了细胞内miR-188-5p的表达,而上清液中miR-188-5p表达增加。探讨miR-188-5p在CIN,HK-2细胞用NC模拟物处理,ioversol,或miR-188-5p模拟物。结果表明,miR-188-5p模拟物的应用降低了细胞凋亡,活性氧和MDA,提高SOD和GSH含量。Further,证实在ioversol处理的HK-2细胞中PTEN的mRNA和蛋白水平上调,并在miR-188-5p给药后下调。双荧光素酶报告基因检测证实PTEN是miR-188-5p的直接靶基因。上述结果表明,循环miR-188-5p有可能作为CIN的预测因子。
Contrast-induced acute kidney injury (CI-AKI), also known as contrast-induced nephropathy (CIN), has become the third leading cause of iatrogenic AKI. Serum creatinine (Scr) is currently used in CIN clinical diagnosis. Patients with increased Scr have developed severe kidney injury, so there is an urgent need to find a bio-marker for CIN early diagnosis. To investigate the changes in circulating microRNA-188-5p (miR-188-5p) after coronary angiography and its predictive value for the CIN occurrence, miR-188-5p expression in CIN rats from the GEO database and CIN patients and control patients from Lianshui People\'s Hospital was analyzed. The results showed that miR-188-5p expression in plasma and renal was higher in CIN group than in control group. Further, a total of 36 CIN patients and 108 non-CIN patients were included. There were significant differences in age, hypertension, diabetes, and contrast agent dosage. After 12 h of contrast agent application, circulating miR-188-5p expression in CIN group was higher than control group. Univariate and multivariate logistic regression analysis showed that age, hypertension, diabetes, contrast media dosage and postoperative miR-188-5p expression were closely related to CIN occurrence. For in vitro experiments, intracellular miR-188-5p expression was decreased with ioversol treatment, while miR-188-5p expression in supernatant was increased. To explore the potential mechanism of miR-188-5p in CIN, HK-2 cells were treated with NC mimic, ioversol, or miR-188-5p mimic. The results showed that the application of miR-188-5p mimic reduced apoptosis, reactive oxygen species and MDA, enhanced SOD and GSH contents. Further, it was confirmed that mRNA and protein levels of PTEN were up-regulated in ioversol-treated HK-2 cells, and down-regulated after miR-188-5p administration. Dual-luciferase reporter gene assay confirmed that PTEN was direct target gene of miR-188-5p. Above results suggest that circulating miR-188-5p has the potential to serve as a predictor of CIN.