Beneficial Effect of Glucose Control on Atherosclerosis Progression in Diabetic ApoE(-/-) Mice: Shown by Rage Directed Imaging.
Beneficial Effect of Glucose Control on Atherosclerosis Progression in Diabetic ApoE(-/-) Mice: Shown by Rage Directed Imaging.
复制标题
血糖控制对糖尿病 ApoE(-/-) 小鼠动脉粥样硬化进展的有益影响：通过愤怒定向成像显示。
DOI：
10.1155/2014/695391
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Johnson,LynneL
中科院分区：
文献类型：
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作者：
Tekabe,Yared;Kollaros,Maria;Li,Qing;Zhang,Geping;Li,Chong;Schmidt,AnnMarie;Johnson,LynneL
目的：晚期糖化终末产物受体(RAGE)在糖尿病动脉粥样硬化形成中起重要作用。方法和结果：33只apoE−/−糖尿病小鼠接受链脲佐菌素治疗，6周后15只开始胰岛素治疗。研究期间测得的血糖平均值：治疗组为14 0±2 3 mg/dL，未治疗组为35 4±14 mg/dL。15 后，30只 小鼠注射99mTC-RAGE，3只注射99mTC-非免疫球蛋白，均注射CT造影剂，行SPECT/CT显像。在尸检时，称量、计数和切片近端主动脉，并计算每克注射剂量的百分比(%ID/g)。合并后的SPECT/CT扫描显示，治疗组小鼠动脉的示踪剂摄取率较低，分别为3.15±1.82×10−3和8.69±4.58×10−3%ID(P=0.001)。治疗组病变面积百分比(14.3±7.8%)小于对照组(29.5±10.9%)(P=0.03)。扫描的RAGE摄取率(%ID)与动脉粥样硬化的RAGE定量染色及%ID/g相关(R=0.6887；P=0.0 1)。治疗组病灶大小(横截面积百分比)较小(14.3±7.8%比29.5±10.9%)(P=0.03)。结论：这些结果支持抑制RAGE对减少糖尿病动脉粥样硬化并发症的重要性，以及分子成像对评估治疗效果的价值。
Objective.Receptor for advanced glycated endproducts (RAGE) plays an important role in atherogenesis in diabetes. We imaged RAGE to investigate the effect of glucose control to suppress RAGE and reduce atherosclerosis in apolipoprotein E null (apoE−/−) diabetic mice.Methods and Results.Thirty‐three apoE−/−mice received streptozotocin and 6 weeks later 15 began treatment with insulin implants. Blood glucose measurements during study averaged: 140 ± 23 mg/dL (treated) and 354 ± 14 mg/dL (untreated). After 15 wk 30 mice were injected with99mTc‐anti‐RAGE, 3 with99mTc‐nonimmune IgG, and all with CT contrast agent and underwent SPECT/CT imaging. At necropsy, the proximal aorta was weighed, counted, and sectioned and the % injected dose per gram (%ID/g) was calculated. From the merged SPECT/CT scans, tracer uptake localized to arteries was lower in the treated mice: 3.15 ± 1.82 × 10−3versus 8.69 ± 4.58 × 10−3%ID (P= 0.001). Percent cross‐sectional lesion area was smaller in the treated (14.3 ± 7.8% versus 29.5 ± 10.9%) (P= 0.03). RAGE uptake on scans (%ID) correlated with quantitative RAGE staining in the atheroma and with %ID/g (R= 0.6887;P= 0.01). Lesion size as percent cross‐sectional area was smaller in the treated (14.3 ± 7.8% versus 29.5 ± 10.9%) (P= 0.03). RAGE uptake on scans (%ID) correlated with quantitative RAGE staining in the atheroma and with %ID/g (R= 0.6887;P= 0.01).Conclusions.These results support the importance of suppressing RAGE to reduce atherosclerotic complications of diabetes and value of molecular imaging to assess treatment effect.