Ma Long, Wu Kun, Liu Kun, Gu Shuo, Wang Yi, Xu Zongyuan, Yu Xiangyou, Meng Junsong
Department of Intensive Care Unit, First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, China.
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Zhonghua Yi Xue Za Zhi. 2015 May 19;95(19):1488-92.
Ischemia-reperfusion (I/R) is a main cause of acute kidney injury (AKI). The renal expression profiles of microRNA (miRNA) and time course of their changes after renal I/R were explored to screen acute AKI prognostic-related microRNAs and biomarkers.
The expression profile of miRNA was analyzed for detecting miRNAs in kidney after renal I/R injury. Real-time polymerase chain reaction (PCR) was performed to validate the results of microarray. And the relationship was examined between kidney injury and time course of changes in selected miRNAs.
Twenty-one miRNAs were differentially expressed in kidney of rats with renal I/R injury. And 5 miRNAs had prominent differences. miR-17-5p, miR-21 and miR-106a were selected for further confirmation by quantitative real-time-PCR. And the results were consistent with those of microarry. During early stage (4 h) after I/R, the expression level of miR-17-5p significantly increased (P < 0.05). And it occurred earlier than those of BUN level and plasma concentration of neutrophil gelatinase-associated lipocalin (NGAL). Renal expressions of miR-21 and miR-106a were significantly elevated in ischemia 20 min and 30 min groups at 12 h and 24 h post-reperfusion (P < 0.01). And the trend was in accordance with those of BUN and NGAL.
miR-21, miR-17-5p and miR-106a are differentially expressed during different phases of renal I/R injury. And miR-17-5p is more sensitive than BUN and NGAL so that it is a more ideal biomarker for AKI.
缺血再灌注(I/R)是急性肾损伤(AKI)的主要原因。通过探究肾I/R后肾脏中微小RNA(miRNA)的表达谱及其变化的时间进程,以筛选与急性AKI预后相关的微小RNA和生物标志物。
分析miRNA的表达谱以检测肾I/R损伤后肾脏中的miRNA。采用实时聚合酶链反应(PCR)验证微阵列结果。并检测所选miRNA的变化时间进程与肾损伤之间的关系。
21种miRNA在肾I/R损伤大鼠的肾脏中差异表达。其中5种miRNA有显著差异。选择miR-17-5p、miR-21和miR-106a通过定量实时PCR进一步确认。结果与微阵列结果一致。在I/R后的早期阶段(4小时),miR-17-5p的表达水平显著升高(P<0.05)。且其升高早于血尿素氮(BUN)水平和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的血浆浓度升高。在再灌注后12小时和24小时,缺血20分钟和30分钟组中miR-21和miR-106a的肾脏表达显著升高(P<0.01)。且该趋势与BUN和NGAL的趋势一致。
miR-21、miR-17-5p和miR-106a在肾I/R损伤的不同阶段差异表达。且miR-17-5p比BUN和NGAL更敏感,因此它是AKI更理想的生物标志物。