Washout rate of Tc-99m MIBI from myocardium in rats with diabetic cardiomyopathy

糖尿病心肌病大鼠心肌Tc-99m MIBI洗出率

• 批准号: 15591308
• 负责人: ISHIHARA Keiichi
• 金额: $ 1.79万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591308/
• 关键词: myocardial damage; doxorubicin; apoptosis; mitochondrial function; diabetic cardiomyopathy; アドリアマイシ; 心筋症; 99m-TC MIBI; 洗い出し率; トロポニンT

To validate reduced Tc-99m MIBI retention in myocardium with damaged mitochondria, myocardial MIBI uptakes of rates administrated with doxorubicin were measured in a fixed interval using gamma camera, and theses serial myocardial Tc-99m MIBI uptakes were compared with serum troponin T level as one of indicators representing ongoing myocardial damage, as well as pathological findings. Twenty Wistar-Kyoto rats of 10 weeks of age were enrolled as induced heart failure and control model animals. Five out of the ten with induced heart failure were subcutaneously administerated with 2mg/kg/W doxorubicin over 7 weeks, and the other five were administrated with the same dose of doxorubicin over 9 weeks. The ten control rats were also divided two clusters (5 each) subcutaneously administrated with the same dose of saline over 7 and 9 weeks, respectively. Blood pressure, hart rate, and body weight of each rat were measured periodically. Three minute acquisition of total and myocardial activities … More were carried out 10, 60, and 120 minutes after 3 MBq MIBI injection, using two-head gamma camera (PRISM 2000) equipped with ultra-high-resolution and pinhole collimators, respectively. Myocardial to total ratios and without ratios from 10 minutes heart to total ratio were compared between doxorubicin and control groups. Following autopsy 120 minutes after Tc-99m MIBI administration, %ID/g (percentage activity of injected dose) of heart as well as serum troponin T level were measured. Histologic scoring index by Herman and Ferrans for doxorubicin cardiomyopathy was estimated with grading on a scale of 0-4 on the basis of the number of myocytes showing cyotplasmic vacuolization and myofibrillar loss. There were significant differences of blood pressure, heart rate, and body weight after 8 weeks between doxorubicin and control groups, suggesting successful preparation for heart failure models in the former group. %ID/g of myocardium and heart to total ratios in doxorubicin group were significant lower than those in control, and washout ratios in doxorubicin group showed significantly greater values compared with those in control. All in doxorubicin group and two in control showed positive in serum troponin level, representing histologic damage of myocardium. Serum troponin T showed significant negative correlation with 10, 60, and 120 minutes heart to total ratios, respectively. Positive and negative correlation of histologic score were obtained significantly with 120 minutes heat to total ratios and 120 minutes washout ratios, respectively. Tc-99m MIBI retention in mitochondria closely related with ongoing myocardial damage in doxorubicin cardiomyopathy. Moreover, correlation of Tc-99m MIBI washout with apoptosis detection accomplished with Annexin V would indicate relationship between Tc-99m MIBI washout and mitochondrial function. On the other hand, no significant differenced were obtained between rats with diabetic cardiomyopathy administrated streptoxotocin and controls in spite of significantly decreased myocardial uptakes of Tc-99m MIBI, suggesting different mechanism between diabetic and doxorubicin heart faiuler. Less

为了验证线粒体受损心肌中 Tc-99m MIBI 滞留的减少，使用伽马相机以固定间隔测量阿霉素给药率的心肌 MIBI 摄取，并将这些连续心肌 Tc-99m MIBI 摄取与血清肌钙蛋白 T 水平进行比较，作为代表持续心肌损伤以及病理学指标之一 调查结果。选取 20 只 10 周龄的 Wistar-Kyoto 大鼠作为诱导心力衰竭和对照模型动物。 10名诱发心力衰竭的患者中，有5名患者皮下注射2mg/kg/W阿霉素7周，另外5名患者皮下注射相同剂量的阿霉素9周。十只对照大鼠也被分为两组（每组 5 只），分别在 7 周和 9 周内皮下注射相同剂量的盐水。定期测量每只大鼠的血压、心率和体重。注射 3 MBq MIBI 后 10、60 和 120 分钟，使用配备超高分辨率和针孔准直器的双头伽玛相机 (PRISM 2000) 分别在三分钟内采集总活动和心肌活动。比较阿霉素组和对照组之间的心肌与总比率以及10分钟心脏与总比率的比率。 Tc-99m MIBI施用后120分钟进行尸检后，测量心脏的%ID/g（注射剂量的活性百分比）以及血清肌钙蛋白T水平。 Herman 和 Ferrans 对阿霉素心肌病的组织学评分指数根据显示细胞质空泡化和肌原纤维损失的肌细胞数量按 0-4 级分级进行估计。 8周后阿霉素组和对照组的血压、心率和体重存在显着差异，表明前者成功制备了心力衰竭模型。阿霉素组的心肌％ID/g和心脏占总比率显着低于对照组，并且阿霉素组的洗出率与对照组相比显着更高。阿霉素组和对照组2例血清肌钙蛋白水平均呈阳性，代表心肌组织学损伤。血清肌钙蛋白 T 分别与 10 分钟、60 分钟和 120 分钟心脏与总心脏比率呈显着负相关。组织学评分分别与 120 分钟加热与总比率和 120 分钟洗脱比率显着呈正相关和负相关。 Tc-99m MIBI 在线粒体中的滞留与阿霉素心肌病中持续的心肌损伤密切相关。此外，Tc-99m MIBI 清洗与用膜联蛋白 V 完成的细胞凋亡检测的相关性将表明 Tc-99m MIBI 清洗与线粒体功能之间的关系。另一方面，尽管心肌对 Tc-99m MIBI 的摄取显着降低，但服用链脲佐菌素的糖尿病心肌病大鼠与对照组之间没有显着差异，这表明糖尿病和阿霉素心力衰竭之间存在不同的机制。较少的