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

为验证线粒体损伤心肌中Tc-99 mMIBI滞留减少的可能性，用γ照相机在固定时间间隔内测定阿霉素给药大鼠心肌的MIBI摄取量，并将这些连续的心肌Tc-99 mMIBI摄取量与血清肌钙蛋白T水平（作为心肌损伤的指标之一）以及病理结果进行比较。将20只10周龄的Wistar-Kyoto大鼠作为诱导的心力衰竭模型动物和对照动物。10只心衰大鼠中5只用阿霉素2 mg/kg/W皮下注射7周，另5只用阿霉素2 mg/kg/W皮下注射9周。10只对照大鼠也分为两组（每组5只），分别在7周和9周内皮下注射相同剂量的生理盐水。定期测量每只大鼠的血压、哈特率和体重。三分钟采集总活动和心肌活动 ...更多信息 分别使用配备有超高分辨率和针孔准直器的双头伽马照相机（PRISM 2000）在3 MBq MIBI注射后10、60和120分钟进行。比较多柔比星组和对照组之间的心肌与总比率和10分钟心脏与总比率的非比率。给药后120分钟剖检，测定心肌%ID/g（注射剂量的活性百分比）和血清肌钙蛋白T（cTnT）水平。根据显示细胞质空泡化和肌原纤维丢失的肌细胞数量，采用0-4级量表评估多柔比星心肌病的赫尔曼和费兰斯组织学评分指数。8周后，阿霉素组大鼠血压、心率、体重与对照组比较差异有统计学意义（P < 0. 05），阿霉素组成功制备心力衰竭模型。阿霉素组心肌的%ID/g和心脏占总体积的比值显著低于对照组，洗脱率显著高于对照组。阿霉素组和对照组各2例血清肌钙蛋白均呈阳性，提示心肌组织学损害。血清肌钙蛋白T分别与10分钟、60分钟和120分钟心脏与总比率呈显著负相关。组织学评分分别与120分钟总热量比和120分钟洗脱率呈显著正相关和负相关。Tc-99 mMIBI在线粒体中的滞留与阿霉素心肌病的持续心肌损伤密切相关。此外，Tc-99 m MIBI洗脱与用Annexin V完成的细胞凋亡检测的相关性将表明Tc-99 m MIBI洗脱与线粒体功能之间的关系。另一方面，尽管糖尿病心肌病大鼠心肌摄取Tc-99 m-MIBI显著降低，但链脲佐菌素组与对照组之间无显著差异，提示糖尿病和阿霉素心肌衰竭的机制不同。少