BackgroundThe neurotoxic potential of gadolinium (Gd)‐based contrast agents (GBCAs) retention in the brains of patients with type 2 diabetes mellitus (T2DM) is unclear.PurposeTo determine the deposition and clearance of GBCAs in T2DM rats and the mechanism by which Gd enhances nucleotide‐binding oligomerization domain‐3 (NLRP3) inflammasome activation.Study TypeCross‐sectional, prospective.Animal Model104 T2DM male Wistar rats.Field Strength/Sequence9.4‐T, T1‐weighted fast spin echo sequence.AssessmentT2DM (male Wistar rats, n = 52) and control group (healthy, male Wistar rats, n = 52) rats received saline, gadodiamide, Gd‐diethylenetriaminepentaacetic acid, and gadoterate meglumine for four consecutive days per week for 7 weeks. The distribution and clearance of Gd in the certain brain were assessed by MRI (T1 signal intensity and relaxation rate R1, on the last day of each week), inductively coupled plasma mass‐spectroscopy, ultraperformance liquid chromatography mass spectrometry, and transmission electron microscopy. Behavioral tests, histopathological features, and the effects of GBCAs on neuroinflammation were also analyzed.Statistical TestsOne‐way analysis of variance, bonferroni method, and unpaired t‐test. A P‐value <0.05 was considered statistically significant.ResultsThe movement distance and appearance time in the open field test of the T2DM rats in the gadodiamide group were significantly shorter than in the other groups. Furthermore, the expression of NLRP3, Pro‐Caspase‐1, interleukin‐1β (IL‐1β), and apoptosis‐associated speck‐like protein containing a CARD protein in neurons was significantly higher in the gadodiamide group than in the saline group, as shown by Western blot. Gadodiamide also induced differentiation of microglia into M1 type, decreased the neuronal mitochondrial membrane potential, and significantly increased neuronal apoptosis from flow cytometry.Data ConclusionT2DM may affect both the deposition and clearance of GBCAs in the brain. Informed by the T2DM model, gadodiamide could mediate the neuroinflammatory response by NLRP3 inflammasome activation.Level of Evidence1Technical EfficacyStage 1

中文翻译：

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重复使用钆基 MRI 造影剂后 2 型糖尿病大鼠大脑中钆滞留对神经生物学和 NLRP3 炎症小体激活的影响

背景钆（Gd）基造影剂（GBCA）在2型糖尿病（T2DM）患者脑内滞留的神经毒性潜力尚不清楚。目的确定GBCA在T2DM大鼠体内的沉积和清除以及Gd增强的机制核苷酸结合寡聚化结构域 3 (NLRP3) 炎性体激活。研究类型横断面，前瞻性。动物模型 104 只 T2DM 雄性 Wistar 大鼠。场强/序列9.4-T，T1 加权快速自旋回波序列。评估 T2DM（雄性 Wistar 大鼠，n= 52）和对照组（健康的雄性 Wistar 大鼠，n= 52) 大鼠每周连续四天接受盐水、钆二胺、Gd-二亚乙基三胺五乙酸和钆酸葡甲胺治疗，持续 7 周。通过MRI（每周最后一天的T1信号强度和弛豫率R1）、电感耦合等离子体质谱、超高效液相色谱质谱和透射电子显微镜评估Gd在特定脑中的分布和清除率。还分析了行为测试、组织病理学特征以及 GBCA 对神经炎症的影响。统计测试单向方差分析、bonferroni 方法和未配对方法t-测试。A磷‐值<0.05为有统计学意义。结果钆双胺组T2DM大鼠在旷场试验中的运动距离和出现时间明显短于其他组。此外，钆双酰胺组神经元中 NLRP3、Pro-Caspase-1、白介素-1β (IL-1β) 和包含 CARD 蛋白的凋亡相关斑点样蛋白的表达显着高于盐水组，如下所示通过蛋白质印迹显示。流式细胞仪显示，钆双酰胺还诱导小胶质细胞分化为M1型，降低神经元线粒体膜电位，并显着增加神经元凋亡。数据结论T2DM可能影响脑内GBCA的沉积和清除。根据T2DM模型，钆双胺可以通过NLRP3炎症小体激活介导神经炎症反应。证据级别1技术功效阶段1