Quantitative characterization of glomerular fibrosis with magnetic resonance imaging: a feasibility study in a rat glomerulonephritis model.

Quantitative characterization of glomerular fibrosis with magnetic resonance imaging: a feasibility study in a rat glomerulonephritis model.
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磁共振成像对肾小球纤维化的定量表征:大鼠肾小球肾炎模型的可行性研究。

DOI:
10.1152/ajprenal.00529.2017
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发表时间:
2018
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
Zhang,JeffL
Zhang,JeffL
中科院分区:
--
文献类型:
--
作者:
Conlin,ChristopherC;Huang,Yufeng;Gordon,BrianAdamJamison;Zhang,JeffL

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肾小球纤维化发生在多种肾脏疾病的早期阶段,包括高血压和糖尿病肾病。传统的肾小球纤维化评估依赖于肾活检,这是侵入性的,不能反映血液灌流等生理方面。在这项研究中,我们试图利用磁共振成像(MRI)评估不同程度肾小球纤维化时皮质血流灌注和微结构的潜在变化。采用注射抗Thy-1单抗OX-7促进系膜细胞外基质增殖的方法建立大鼠肾小球纤维化模型。对诱导后第5天的6只大鼠和第12天的5只大鼠,我们在3Tesla磁共振扫描仪上测量了肾皮质的血流灌注和自旋-自旋松弛时间(T2)。T2反映了组织的微结构变化。通过组织学分析和蛋白尿评价肾小球纤维化的严重程度。4只非肝纤维化大鼠作为对照组。对照组PAS阳性面积为肾小球总面积的22 ± 1%,第5天和第12天纤维化组分别为56 ± 12%和45 ± 10%(P<0.01)。3组(对照组、注射OX-7后第5天和第12天)皮质血流灌注量分别为7.27 ± 2.54、3.78 ± 2.17和3.32 ± 2.62ml·−·g−1,分别为75.2 ± 4.6、84.1 ± 3.0和87.9 ± 5.6 ms(P&lt;0.01)。总之,肾小球系膜细胞中细胞外基质的增殖严重减少了通过肾小球的血流,并改变了皮质微结构以增加皮质T2。MRI测量的参数被证明是表征肾小球纤维化的敏感标志物。
Glomerular fibrosis occurs in the early stages of multiple renal diseases, including hypertensive and diabetic nephropathy. Conventional assessment of glomerular fibrosis relies on kidney biopsy, which is invasive and does not reflect physiological aspects such as blood perfusion. In this study, we sought to assess potential changes of cortical perfusion and microstructure at different degrees of glomerular fibrosis using magnetic resonance imaging (MRI). A rat model of glomerular fibrosis was induced by injecting anti-Thy-1 monoclonal antibody OX-7 to promote mesangial extracellular matrix proliferation. For six rats onday 5and five rats onday 12after the induction, we measured renal cortical perfusion and spin-spin relaxation time (T2) in a 3-Tesla MRI scanner. T2reflects tissue microstructural changes. Glomerular fibrosis severity was evaluated by histological analysis and proteinuria. Four rats without fibrosis were included as controls. In the control rats, the periodic acid-Schiff (PAS)-positive area was 22 ± 1% of total glomerular tuft, which increased significantly to 56 ± 12% and 45 ± 10% in theday 5andday 12fibrotic groups, respectively (P< 0.01). For the three groups (control,day 5, andday 12after OX-7 injection), cortical perfusion was 7.27 ± 2.54, 3.78 ± 2.17, and 3.32 ± 2.62 ml·min−1·g−1, respectively, decreasing with fibrosis severity (P< 0.01), and cortical T2was 75.2 ± 4.6, 84.1 ± 3.0, and 87.9 ± 5.6 ms, respectively (P< 0.01). In conclusion, extracellular matrix proliferation in glomerular mesangial cells severely diminished blood flow through the glomeruli and also altered cortical microstructure to increase cortical T2. The MRI-measured parameters are proven to be sensitive markers for characterizing glomerular fibrosis.
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