Abstract：
BACKGROUND: The neurotoxic potential of gadolinium (Gd)-based contrast agents (GBCAs) retention in the brains of patients with type 2 diabetes mellitus (T2DM) is unclear.
OBJECTIVE: To 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.
METHODS: Cross-sectional, prospective.
UNASSIGNED: 104 T2DM male Wistar rats.
UNASSIGNED: 9.4-T, T1-weighted fast spin echo sequence.
RESULTS: T2DM (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.
METHODS: One-way analysis of variance, bonferroni method, and unpaired t-test. A P-value <0.05 was considered statistically significant.
RESULTS: The 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.
CONCLUSIONS: T2DM 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.
METHODS: 1 TECHNICAL EFFICACY: Stage 1.
OBJECTIVE: To 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.
METHODS: Cross-sectional, prospective.
UNASSIGNED: 104 T2DM male Wistar rats.
UNASSIGNED: 9.4-T, T1-weighted fast spin echo sequence.
RESULTS: T2DM (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.
METHODS: One-way analysis of variance, bonferroni method, and unpaired t-test. A P-value <0.05 was considered statistically significant.
RESULTS: The 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.
CONCLUSIONS: T2DM 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.
METHODS: 1 TECHNICAL EFFICACY: Stage 1.
摘要：
背景：基于钆(Gd)的造影剂(GBCA)滞留在2型糖尿病(T2DM)患者脑中的神经毒性潜力尚不清楚。
目的：探讨GBCA在T2DM大鼠体内的沉积和清除以及Gd增强核苷酸结合寡聚化结构域-3(NLRP3)炎性体激活的机制。
方法：横截面，前瞻性。
■104只T2DM雄性Wistar大鼠。
■9.4-T，T1加权快速自旋回波序列。
结果：T2DM（雄性Wistar大鼠，n=52）和对照组（健康，雄性Wistar大鼠,n=52）大鼠接受生理盐水，gadodiamide,Gd-二亚乙基三胺五乙酸，和gadoterate葡甲胺，每周连续四天，共7周。通过MRI评估Gd在某些大脑中的分布和清除（T1信号强度和松弛率R1，在每周的最后一天），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。行为测试,组织病理学特征,并分析了GBCAs对神经炎症的影响。
方法：单向方差分析，bonferroni方法，和不成对t检验。P值<0.05被认为具有统计学意义。
结果：gadodiamide组T2DM大鼠在开放视野试验中的运动距离和出现时间明显短于其他组。此外，NLRP3、Caspase-1、白细胞介素-1β(IL-1β)的表达,神经元中含有CARD蛋白的凋亡相关斑点样蛋白在gadodiamide组明显高于盐水组，如Westernblot所示。加多二酰胺还诱导小胶质细胞分化为M1型，降低了神经元线粒体膜电位，流式细胞术显示神经元凋亡显著增加。
结论：T2DM可能影响脑内GBCA的沉积和清除。由T2DM模型通知，gadiamide可以通过激活NLRP3炎性体介导神经炎症反应。
方法：1技术效果：第一阶段。
目的：探讨GBCA在T2DM大鼠体内的沉积和清除以及Gd增强核苷酸结合寡聚化结构域-3(NLRP3)炎性体激活的机制。
方法：横截面，前瞻性。
■104只T2DM雄性Wistar大鼠。
■9.4-T，T1加权快速自旋回波序列。
结果：T2DM（雄性Wistar大鼠，n=52）和对照组（健康，雄性Wistar大鼠,n=52）大鼠接受生理盐水，gadodiamide,Gd-二亚乙基三胺五乙酸，和gadoterate葡甲胺，每周连续四天，共7周。通过MRI评估Gd在某些大脑中的分布和清除（T1信号强度和松弛率R1，在每周的最后一天），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。行为测试,组织病理学特征,并分析了GBCAs对神经炎症的影响。
方法：单向方差分析，bonferroni方法，和不成对t检验。P值<0.05被认为具有统计学意义。
结果：gadodiamide组T2DM大鼠在开放视野试验中的运动距离和出现时间明显短于其他组。此外，NLRP3、Caspase-1、白细胞介素-1β(IL-1β)的表达,神经元中含有CARD蛋白的凋亡相关斑点样蛋白在gadodiamide组明显高于盐水组，如Westernblot所示。加多二酰胺还诱导小胶质细胞分化为M1型，降低了神经元线粒体膜电位，流式细胞术显示神经元凋亡显著增加。
结论：T2DM可能影响脑内GBCA的沉积和清除。由T2DM模型通知，gadiamide可以通过激活NLRP3炎性体介导神经炎症反应。
方法：1技术效果：第一阶段。
