^(131)Ⅰ-大黄素和^(131)Ⅰ-大黄素酸的坏死靶向性及成像坏死心肌的研究  

Research on the necrosis target and imaging of necrotic myocardium of ^(131)Ⅰ-emodin and ^(131)Ⅰ-emodic acid

作　　者：王琴[1,2] 张东建[2] 李进典[2,3] 徐梦丹[2] 廖红[4] 殷志琦[3] 张健[2] 

机构地区：[1]南京中医药大学药学院,南京210023 [2]江苏省中医药研究院转化医学实验室,南京210028 [3]中国药科大学天然药物化学教研室,南京210009 [4]中国药科大学江苏省新药筛选重点实验室,南京210009

出　　处：《中国药科大学学报》2016年第2期235-241,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81473120;No.81501536);江苏省新药筛选重点实验室开放课题资助项目(No.JKLDS2015KF-02);常州四药.医院药学科研基金资助项目(No.2014YX011)~~

摘　　要：探讨^(131)Ⅰ-大黄素和^(131)Ⅰ-大黄素酸的坏死靶向性及成像坏死心肌的潜能。用放射性^(131)Ⅰ标记大黄素、大黄素酸,在小鼠肌肉坏死和大鼠心肌梗死(MⅠ)模型上评估这两个示踪剂的坏死靶向性及成像潜能。分别在给药2、12和24 h后处死小鼠,并用γ-计数器测量主要脏器、坏死肌肉的放射量。给药6 h后,SPECT/CT成像大鼠梗死心肌,测量组织分布,并对心脏切片进行病理学分析。小鼠分布数据表明^(131)Ⅰ-大黄素和^(131)Ⅰ-大黄素酸具有良好的坏死靶向性,同时从正常组织清除较快。SPECT/CT图像显示这两个化合物在MⅠ大鼠的心脏部位有高摄取("热点"成像),而在假手术大鼠的心脏区域没有明显的摄取。磷屏定量数据表明:^(131)Ⅰ-大黄素和^(131)Ⅰ-大黄素酸的坏死/正常心肌比分别为9.72和13.14。以上结果说明这两个示踪剂都具有坏死靶向性及成像坏死心肌的潜能。The purpose of this study was to evaluate the necrosis target and imaging potential of necrotic myocardium of（131）I-emodin and（131）I-emodic acid. The iodogen coating method was used to radioiodinate emodin and emodic acid with iodine-131. Mice model of muscular necrosis and rat model of myocardial infarction（ MI） were established to evaluate the necrosis affinity and imaging potential of（131）I-emodin and（131）I-emodic acid. Mice were sacrificed at 2,12 and 24 h after injection respectively. The radioactive uptake in major organs and necrotic muscle were calculated by a γ-counter. At 6 h after administration,SPECT / CT imaging of necrotic myocardium in rats, biodistribution detection, histopathological analysis were applied to evaluate their necrosis affinity and imaging potential. The results of biodistribution from mice demonstrated that（131）I-emodin and（131）I-emodic acid showed peculiar necrosis target and exhibited an obvious clearance of radioactivity from normal organs. On SPECT / CT images,relatively high uptake as a hot spot was shown in the heart of the model rat,while no obvious uptake was observed in the heart of the control rat. The radioactivity ratios of necrotic to normal myocardium of（131）I-emodin and（131）I-emodic acid amounted up to 9. 72 and 13. 14 by quantitative autoradiography analysis,respectively. These results suggested that（131）I-emodin and（131）I-emodic acid possess the necrosis target and imaging potential of necrotic myocardium.

关 键 词：(131)Ⅰ-大黄素 (131)Ⅰ-大黄素酸 坏死靶向性 心肌梗死 成像 

分 类 号：R965[医药卫生—药理学]