Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury
Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury
复制标题
DOI：
10.1080/15287394.2017.1299655
复制
发表时间：
2017-01-01
影响因子：
2.6
通讯作者：
Kim, Hyung Sik
中科院分区：
文献类型：
--
作者：
Kim, Kyeong Seok;Yang, Hun Yong;Kim, Hyung Sik
急性肾损伤（阿基）与患者死亡率增加相关，但目前尚没有临床可用的疾病检测生物标志物。最近，一种新的生物标志物，硒结合蛋白1（SBP 1），被确定为检测肾毒性的蛋白质组学分析。本研究的目的是使用顺铂或缺血/再灌注（I/R）等动物模型评估尿SBP 1水平作为阿基早期检测的敏感性。将Sprague-Dawley大鼠用顺铂（6 mg/kg，一次i. p.）并在处理后1、3或5天处死。通过用微血管夹双侧闭塞双肾45分钟实现缺血，并通过组织颜色的变化进行目视验证。再灌注后，在9、24和48小时间隔收集尿液样品。通过蛋白质印迹分析测量基于蛋白质的生物标志物的尿排泄。在顺铂处理的大鼠中，在第1天观察到轻度组织病理学改变，在第3天变得严重。第3天血尿素氮（BUN）和血清肌酐（SCr）水平显著升高。在药物治疗后第3天和第5天，尿中SBP 1、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和金属蛋白酶组织抑制剂-1（TIMP-1）的排泄水平显著升高。在溶剂处理的I/R组中，与假手术组相比，血清BUN和SCr水平以及AST活性显著增加。I/R后尿SBP 1和NGAL排泄量明显增加。比较阿基患者和正常人尿中排出的SBP 1、NGAL、TIMP-1和KIM-1蛋白水平。在这些蛋白质中，与正常受试者相比，在阿基患者的尿液中观察到SBP 1显著升高。根据受试者-操作者曲线（ROC），SBP 1显示出比SCr、BUN、总蛋白和葡萄糖水平更高的曲线下面积（AUC）评分。特别是，SBP 1蛋白很容易在少量尿液中检测到，无需纯化。因此，数据表明，尿排泄的SBP 1可能是有用的作为一个可靠的生物标志物，用于早期诊断患者的阿基。
Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.