采用动脉自旋标记在转化鼠模型中对急性和慢性肾移植排斥反应的灌注变化进行纵向评估。

Longitudinal evaluation of perfusion changes in acute and chronic renal allograft rejection using arterial spin labeling in translational mouse models.

机构信息

Radiology, Hannover Medical School, Germany.

Nephrology, Hannover Medical School, Germany.

出版信息

J Magn Reson Imaging. 2017 Dec;46(6):1664-1672. doi: 10.1002/jmri.25713. Epub 2017 Mar 25.

DOI:10.1002/jmri.25713

PMID:28342287

Abstract

PURPOSE

To examine the longitudinal changes of renal perfusion due to acute and chronic renal allograft rejection by using arterial spin labeling (ASL) MRI in translational mouse models of isogenic and allogenic kidney transplantation (ktx).

MATERIALS AND METHODS

Acute rejection was induced by allogenic ktx of C57BL/6 (B6)-kidney grafts to BALB/c-recipients with prolonged cold ischemia (CIT) of 60 minutes (n = 13). To induce chronic rejection BALB/c-kidneys were transplanted into B6-recipients with short CIT of 30 minutes (n = 22). Isogenic grafts without rejection (n = 14 with prolonged, n = 9 with short CIT) and normal kidneys (n = 22) were used for comparison. Perfusion was measured on a 7T small-animal magnetic resonance imaging (MRI) scanner using flow-sensitive alternating inversion recovery (FAIR) ASL-sequences at day 1 and 6 (acute) or at week 3 and 6 (chronic) after surgery. Histological analyses of grafts included inflammation, vascular changes, and fibrosis.

RESULTS

In the acute ktx model, ASL showed perfusion impairment in isogenic and allogenic kidney grafts. Perfusion of allografts further decreased until day 6 and remained stable in isografts without rejection (allogenic ktx 62 ± 21 vs. isogenic ktx 181 ± 39 ml/min/100g, P < 0.01). In the chronic ktx model, perfusion in isografts was similar to normal kidneys over the entire observation period. Perfusion was severely reduced in allografts compared to isografts (week 3: 28 ± 7 vs. 310 ± 46 ml/min/100g, P < 0.001, week 6: 32 ± 5 vs. 367 ± 72 ml/min/100g, P < 0.001). Histological analysis revealed severe inflammation, vascular occlusion, and rejection in allografts. Chronic rejection grafts showed endothelialitis, peritubular capillaritis, interstitial fibrosis, and tubular atrophy.

CONCLUSION

ASL allows longitudinal assessment of renal perfusion impairment due to acute and chronic renal allograft rejection in translational mouse models.

LEVEL OF EVIDENCE

2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1664-1672.

摘要

目的

通过动脉自旋标记（ASL）MRI 检查同种和异种肾移植（ktx）转化小鼠模型中急性和慢性肾移植排斥反应引起的肾灌注的纵向变化。

材料和方法

通过将 C57BL/6（B6）-供体肾脏移植到 BALB/c 受体中，并用 60 分钟的长时间冷缺血（CIT）（n=13）诱导急性排斥反应。为了诱导慢性排斥反应，BALB/c 肾脏被移植到 CIT 为 30 分钟的 B6 受体中（n=22）。未排斥的同种移植物（n=14 个，CIT 时间较长，n=9 个，CIT 时间较短）和正常肾脏（n=22 个）用于比较。在第 1 天和第 6 天（急性）或第 3 周和第 6 天（慢性）手术后，使用血流敏感反转恢复（FAIR）ASL 序列在 7T 小动物磁共振成像（MRI）扫描仪上测量灌注。移植物的组织学分析包括炎症、血管变化和纤维化。

结果

在急性 ktx 模型中，ASL 显示同种和异种肾移植物的灌注受损。同种异体移植物的灌注进一步降低，直到第 6 天，未排斥的同种移植物保持稳定（同种异体 ktx 62±21 vs. 同种异体 ktx 181±39ml/min/100g，P<0.01）。在慢性 ktx 模型中，同种移植物的灌注在整个观察期间与正常肾脏相似。与同种移植物相比，同种异体移植物的灌注严重减少（第 3 周：28±7 vs. 310±46ml/min/100g，P<0.001，第 6 周：32±5 vs. 367±72ml/min/100g，P<0.001）。组织学分析显示同种异体移植物中严重的炎症、血管闭塞和排斥反应。慢性排斥反应移植物表现出内皮炎、肾小管毛细血管炎、间质纤维化和肾小管萎缩。