糖尿病肾病铁沉积的MRI定量研究

Diabetic nephropathy (DN) is one of the leading causes of death in patients with diabetes, and it is also the main cause of chronic renal failure (CRF). The contents of iron and ferritin in renal proximal tubule were significantly increased in DN patients, which stimulate a series of signal pathway of inflammatory reaction, and lead to the glomerular and tubulointerstitial fibrosis as well as extracellular matrix thickening. In the previous study, we found that there were significant differences of the iron contents of renal cortex measured by susceptibility-weighted imaging (SWI) among various stages of DN. Based on above-mentioned reasons, the project group will use the iron contents measured by SWI as the biomarker in DN diagnosis and monitoring response to treatment and evaluate the feasibility and application values. In order to demonstrate our hypothesis, the project group will take the results of atomic absorption spectrophotometer as golden standard to evaluate the correlation between iron contents quantitatively measured by SWI and DN in an animal model. The correlations among renal blood flow, micro-inflammation environments, the alterations of glomeruli and mesenterium and iron contents will be assessed to define the influence factors on iron contents measured by SWI. The sensitivity of iron content measured by SWI in monitoring response to treatment will be demonstrated by evaluating the difference of iron contents before and after administrating deferiprone. By these studies, our hypothesis will be demonstrated. The clinical value of SWI will be explored comprehensively and open up a new way for the imaging research of DN.

糖尿病肾病（DN）是导致糖尿病患者死亡及慢性肾功能衰竭（CRF）的主要原因之一。DN肾近曲小管内铁及铁蛋白含量升高激发炎症信号通路，从而使肾小球、肾小管及其间质出现纤维化及细胞外基质增厚等。我们在前期的工作中发现不同进程的DN患者利用磁敏感成像技术（SWI）计算的肾皮质铁含量存在差异。基于上述理由，项目组拟利用SWI测量DN肾皮质铁含量，将其作为DN诊断及评价疗效的生物学指标，评价其可行性及应用价值。为了论证上述科研假设，项目组将构建DN动物模型，以原子吸收分光光度计结果作为金标准，评价SWI铁定量分析与DN肾皮质铁浓度之间的相关性；比较肾动脉血流、微炎症环境、肾小球及系膜变化与铁含量的相关性，分析SWI铁定量的影响因素；分析去铁酮治疗前后铁含量的变化，论证SWI监测DN疗效的敏感性。通过这些研究论证我们的科研假说，全面评价SWI的临床价值，为DN的影像研究开辟一条新的思路。

糖尿病作为临床常见病，其发病率呈逐年上升趋势。糖尿病肾病是其最严重的慢性微血管并发症，这种进行性的肾衰退与肾脏过量铁沉积有关，铁过载具有显着的促氧化和促炎症作用，进一步加速肾脏损害。因此，准确和有效的评价肾脏过量铁沉积对于监测糖尿病患者的肾脏损害具有重要价值，而非侵入性的检测方法是首选。磁敏感加权成像（SWI）是一种新型MRI技术，其在展示顺磁信号方面优于传统MRI，可以通过测量铁元素的幅度和相位数据间接定量分析铁含量。.本项目的研究内容主要为动物实验。构建对照组和铁剂组模型（经兔后腿肌肉注射铁剂），糖尿病铁剂组（先经兔耳缘静脉注射四氧嘧啶构建糖尿病模型，成功后经兔后腿肌肉注射铁剂）和对照铁剂组模型。应用普鲁士蓝染色观察模型的肾铁沉积分布，比较对照组和铁剂组、糖尿病铁剂组和对照铁剂组的肾皮质角弧度值差异、原子吸收分光光度计所测肾铁含量差异，研究角弧度值与肾铁含量间的相关性。.结果证实：⑴SWI能够评价肾脏过量铁沉积，过量铁主要沉积于肾皮质并使其SWI信号减低，由相位值计算角弧度值可以量化铁沉积。铁剂组8周的角弧度值[0.2023(0.1618，0.2725)]明显高于对照组8周[-0.0112(-0.0529，-0.0014)]（Z=-4.666, P=0.000）。仅铁剂组8周的肾皮质内见明显蓝色铁离子沉积、髓质内见极少量蓝色铁离子沉积；铁剂组8周的肾铁含量（135.3±14.1）mg/kg明显高于对照组8周（75.5±9.8）mg/kg（t=13.938，P=0.000）。铁剂组8周和对照组8周的角弧度值与其所测肾铁含量呈高度正相关（r=0.866，P=0.000）。⑵SWI能够定量评估糖尿病肾脏的铁沉积，糖尿病肾脏的铁沉积较正常肾脏多。糖尿病铁剂组12周的肾皮质角弧度值（0.3911±0.0770）显著高于对照铁剂组12周（0.2238±0.0652）（t=6.229，P=0.000）。普鲁士蓝染色肾皮质糖尿病铁剂组12周见较多蓝染，对照铁剂组12周少量蓝染。糖尿病铁剂组12周的肾铁含量（193.8±10.1）mg/kg显著高于对照铁剂组12周（138.0±12.5）mg/kg（t=12.872，P=0.000）。.本项目系统而全面的研究论证了SWI技术在糖尿病肾脏铁沉积中的价值，为临床评价糖尿病肾病提供了一种全新的选择。