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急性肾损伤:动脉自旋标记监测小鼠肾灌注损伤——与组织病理学结果和肾功能的比较。

Acute kidney injury: arterial spin labeling to monitor renal perfusion impairment in mice-comparison with histopathologic results and renal function.

机构信息

From the Department of Radiology (K.H., M.G., D.H., F.W.), Department of Nephrology (S.R., X.L., H.H., F.G.), and Institute for Animal Science (M. Meier), Hannover Medical School, Carl-Neuberg-Str 1, 30625 Hannover, Germany; and Alberta Transplant Applied Genomics Centre, University of Alberta, Edmonton, Alberta, Canada (M. Mengel).

出版信息

Radiology. 2014 Jan;270(1):117-24. doi: 10.1148/radiol.13130367. Epub 2013 Oct 28.

DOI:10.1148/radiol.13130367
PMID:24023073
Abstract

PURPOSE

To determine if arterial spin-labeling (ASL) magnetic resonance (MR) imaging can show serial changes in renal perfusion in mice with ischemia-induced acute kidney injury (AKI) and to compare imaging results with those of renal histologic examination and inulin and para-aminohippuric acid (PAH) clearance.

MATERIALS AND METHODS

In this animal care committee-approved study, AKI was induced in C57Bl/6 mice (n = 26) by clamping the right renal pedicle for 35 minutes for moderate (n = 16) or 45 minutes (n = 11) for severe AKI. Renal perfusion was measured in 10 animals with moderate and seven animals with severe AKI before and at five time points 1-28 days after surgery by using ASL with a 7-T MR imaging unit. Kidney volume loss and histologic evidence of acute tubular injury were assessed. Inulin and PAH clearance was determined in four animals with moderate and six animals with severe AKI to evaluate renal function and plasma flow for statistical analysis. Repeated measures analysis of variance, unpaired t tests, and correlation analysis were used.

RESULTS

Renal perfusion values at day 7 were significantly reduced after moderate (56% ± 8; P < .01) and severe (33% ± 6; P < .001) AKI compared with presurgery values. Renal perfusion had returned to baseline levels at day 21 after moderate (96% ± 14) and remained compromised until day 28 after severe (46 % ± 9; P < .05) AKI. At day 28, for moderate versus severe AKI, kidney volume (84% ± 6 vs 60% ± 5; P < .05), degree of tubular injury (5.6% ± 1.8 vs 15.8% ± 2.4; P < .01), and inulin and para-aminohippuric acid clearance (47.5 µL/min ± 5.6 vs 7.3 µL/min ± 2.7; P < .001 and 100.8 µL/min ± 24.3 vs 4.8 µL/min ± 1.0; P < .001, respectively) were significantly different. Relative renal perfusion at days 7-28 significantly correlated with kidney volume loss (P < .01) and tubular injury (P < .05) 4 weeks after AKI.

CONCLUSION

ASL allows evaluation of renal perfusion impairment associated with kidney volume loss and histologic changes after AKI in mice and may serve as a noninvasive biomarker for AKI.

摘要

目的

确定动脉自旋标记(ASL)磁共振(MR)成像是否可显示缺血性急性肾损伤(AKI)小鼠的肾灌注的系列变化,并将成像结果与肾组织学检查和菊粉及对氨基马尿酸(PAH)清除率进行比较。

材料与方法

在这项经动物护理委员会批准的研究中,通过夹闭右侧肾蒂 35 分钟(中重度 AKI,n=16)或 45 分钟(重度 AKI,n=11),在 C57Bl/6 小鼠中诱导 AKI。在手术前和术后 1-28 天的 10 只中度 AKI 动物和 7 只重度 AKI 动物中,使用 7T MR 成像仪进行 ASL 测量,评估肾灌注。评估肾脏体积损失和急性肾小管损伤的组织学证据。在 4 只中度 AKI 动物和 6 只重度 AKI 动物中,通过菊粉和 PAH 清除率评估肾功能和血浆流量,进行统计分析。使用重复测量方差分析、非配对 t 检验和相关分析。

结果

中度(56%±8;P<.01)和重度(33%±6;P<.001)AKI 后第 7 天的肾灌注值与术前值相比显著降低。中度 AKI 在第 21 天恢复至基线水平(96%±14),重度 AKI 则持续至第 28 天(46%±9;P<.05)。在第 28 天,与重度 AKI 相比,中度 AKI 的肾脏体积(84%±6 比 60%±5;P<.05)、肾小管损伤程度(5.6%±1.8 比 15.8%±2.4;P<.01)和菊粉及 PAH 清除率(47.5μL/min±5.6 比 7.3μL/min±2.7;P<.001 和 100.8μL/min±24.3 比 4.8μL/min±1.0;P<.001)均显著不同。AKI 后 4 周,肾灌注相对值与肾脏体积损失(P<.01)和肾小管损伤(P<.05)显著相关。

结论

ASL 可评估与肾体积损失和 AKI 后组织学变化相关的肾灌注损害,可能作为 AKI 的非侵入性生物标志物。

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