使用功能磁共振成像评估大鼠急性同种异体移植排斥模型。

Using functional magnetic resonance imaging to evaluate an acute allograft rejection model in rats.

作者信息

Zeng Song, Liang Lu, Zhang Qiang, Xu Yue, Tang Hao, Zhang Zijian, Zhang Xiaodong, Jiang Tao, Hu Xiaopeng

机构信息

Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China; Institute of Urology, Capital Medical University, Beijing, China.

Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

出版信息

Magn Reson Imaging. 2019 May;58:24-31. doi: 10.1016/j.mri.2019.01.006. Epub 2019 Jan 7.

DOI:10.1016/j.mri.2019.01.006

PMID:30630071

Abstract

PURPOSE

To assess the longitudinal changes of allograft pathophysiology by intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) MRI in a rat model of acute renal allograft rejection.

MATERIALS AND METHODS

Acute rejection (AR) was induced by transplantation of Dark Agouti donor kidneys into Lewis recipients (n = 18). A Lewis-Lewis rat syngeneically transplanted (sTX) model served as the control (n = 6). Acute tubular necrosis (n = 6) and acute calcineurin inhibitor toxicity (n = 6) groups were established using Lewis rats. MRI was performed on postoperative day (POD) 1, 4 and 7 in the allogeneically transplanted (aTX) group and on POD4 in the other groups. Histological evaluation and PCR were performed.

RESULTS

After the allogenic transplantation, all MRI parameters of allograft further decreased until POD7, and the D and ADC values in the cortex were significantly lower than that in the sTX group (1.03 ± 0.09 vs 1.52 ± 0.09 × 10 mm/s, P < 0.05; 1.21 ± 0.03 vs 1.78 ± 0.07 × 10 mm/s, P < 0.05). The D*, f and R2* values of the aTX group in the cortex and medulla were significantly lower than those in the sTX group on POD7 (cortex, D*: 25.60 ± 4.78 vs 69.32 ± 9.79 × 10 mm/s, P < 0.05; f: 7.84 ± 1.83 vs 20.34 ± 3.08%, P < 0.05; R2*: 16.61 ± 4.18 vs 31.48 ± 6.43 1/s, P < 0.05; medulla, D*: 13.59 ± 6.08 vs 62.75 ± 9.20 × 10 mm/s, P < 0.05; f: 7.46 ± 1.62 vs 14.68 ± 2.05%, P < 0.05; R2*: 21.59 ± 3.45 vs 39.53 ± 4.34 1/s, P < 0.05). AR grafts presented serve interstitial inflammation, tubulitis and infiltration of T-lymphocytes and macrophages. The MRI parameters, including D, ADC, D*, f and R2*, were significantly correlated with the histological changes, cell infiltration and inflammatory cytokine mRNA levels.

CONCLUSIONS

IVIM coupled with BOLD MRI allows longitudinal assessment of allograft diffusion, perfusion and oxygen consumption impairment caused by acute renal allograft rejection in rat model.

摘要

目的

通过体素内不相干运动（IVIM）和血氧水平依赖性功能磁共振成像（BOLD MRI）评估大鼠急性肾移植排斥模型中同种异体移植肾病理生理学的纵向变化。

材料与方法

将暗褐鼠供体肾移植到Lewis受体大鼠体内诱导急性排斥反应（AR，n = 18）。Lewis-Lewis大鼠同基因移植（sTX）模型作为对照（n = 6）。使用Lewis大鼠建立急性肾小管坏死组（n = 6）和急性钙调神经磷酸酶抑制剂毒性组（n = 6）。在同种异体移植（aTX）组术后第1、4和7天以及其他组术后第4天进行MRI检查。进行组织学评估和聚合酶链反应（PCR）。

结果

同种异体移植后，同种异体移植肾的所有MRI参数在术后第7天前进一步降低，皮质的D值和表观扩散系数（ADC）值显著低于sTX组（1.03 ± 0.09 vs 1.52 ± 0.09×10⁻³mm²/s，P < 0.05；1.21 ± 0.03 vs 1.78 ± 0.07×10⁻³mm²/s，P < 0.05）。术后第7天，aTX组皮质和髓质的D值、灌注分数（f）值和R2值显著低于sTX组（皮质，D*：25.60 ± 4.78 vs 69.32 ± 9.79×10⁻³mm²/s，P < 0.05；f：7.84 ± 1.83 vs 20.34 ± 3.08%，P < 0.05；R2*：16.61 ± 4.18 vs 31.48 ± 6.43 1/s，P < 0.05；髓质，D*：13.59 ± 6.08 vs 62.75 ± 9.20×10⁻³mm²/s，P < 0.05；f：所给英文原文此处有误，应为7.46 ± 1.62 vs 14.68 ± 2.05%，P < 0.05；R2*：21.59 ± 3.45 vs 39.53 ± 4.34 1/s，P < 0.05）。急性排斥反应的移植肾表现为严重的间质炎症、肾小管炎以及T淋巴细胞和巨噬细胞浸润。MRI参数，包括D、ADC、D*、f和R2*，与组织学变化、细胞浸润和炎性细胞因子mRNA水平显著相关。