期刊文献+

^(99)锝~m标记突触结合蛋白I-C2A片段无创性检测易损动脉粥样硬化斑块的实验研究 被引量:6

Noninvasive detection of experimental vulnerable atherosclerotic plaques with ^(99)Tc^m labeled C2A domain of synaptotagmin I
原文传递
导出
摘要 目的利用^(99)锝~m 标记的突触结合蛋白 I-C2A 片段(^(99)Tc^m-Syt I-C2A)作为放射性核素显像剂检测体内易损动脉粥样硬化斑块。方法用基因工程制备突触结合蛋白 I-C2A 片段,2-亚氨基噻吩盐酸盐(2-IT)法进行放射性核素标记,制成^(99)Tc^m-Syt I-C2A。5只新西兰白兔经胆固醇饲料喂养3个月及腹主动脉内皮损伤形成易损动脉粥样硬化斑块模型,另3只作为正常对照组。静脉注射^(99)Tc^m-Syt I-C2A 后进行活体显像,并取出腹主动脉进行体外血管显像和病理检查。结果注射显像剂后2 h,实验组腹主动脉部位放射性摄取明显增高,显影清晰,靶器官/本底(T/B)放射性比值为3.25±0.51。体外显像,腹主动脉亦可见高放射性摄取,与胸主动脉的放射性比值为8.39±1.74。实验组腹主动脉单位质量放射性摄取是正常对照组的12.6倍,是胸主动脉的10.2倍。结论 ^(99)Tc^m-Syt I-C2A 能够与易损粥样硬化斑块特异结合,并进行体外成像,有望成为无创性检测动脉易损粥样硬化斑块的有效方法。 Objective ^99Tc^m labeled C2A domain of synaptotagmin I(^99Tc^m-Syt I-C2A)is used for noninvasive detection of vulnerable atherosclerotic plaque. Methods Recombinant C2A domain of synaptotagmin I,overexpressed in E. Coli, was thiolated with 2-iminothiolane (2-IT) and labeled with ^99Tc^m. Atherosclerotic plaques were produced in 5 rabbits by deendothelialization of the abdominal aorta and the rabbits were fed with cholesterol diet for 3 months. Three rabbits not manipulated served as normal controls. All animals were injected with ^99Tc^m-Syt I-C2A and underwent in vivo imaging thereafter. Aortas were then explanted for ex vivo imaging and histological characterization. Results In deendothelized animals, intense radio-uptake in abdominal aorta, showed by γ camera at 2 h after injection, was visualized and T/B was 3.25 ± 0.51 by ROI measurement, quantitative uptake ratio of abdominal aortas with atheroscleretic lesions to thoracic aortas was 8.39 ± 1.74 in ex vivo imaging. The mean uptake in specimens of abdominal aortas with lesions was 12. 6-fold higher than in control abdominal aortas, and 10. 2-fold higher than in thoracic aortas of deendothelized animals by γ-counter. Conclusion ^99 Tc^m-Syt I-C2A has a high affinity for vulnerable atherosclerotic plaque and is a suitable a gent for the noninvasive detection of vulnerable atherescleretic plaque.
出处 《中华心血管病杂志》 CAS CSCD 北大核心 2007年第2期178-181,共4页 Chinese Journal of Cardiology
基金 国家自然科学基金(30500134)
关键词 动脉硬化 细胞凋亡 放射性核素显像 突触结合蛋白I Atherosclerosis Apoptosis Radionuclide imaging Synaptotagmin I
  • 相关文献

参考文献14

  • 1Naghavi M,Libby P,Falk E,et al.From vulnerable plaque to vulnerable patient:a call for new definitions and risk assessment strategies:Part Ⅰ.Circulation,2003,108 (14):1664-1672.
  • 2胡野,凌志强,单小云.细胞凋亡与心血管疾病//胡野,凌志强,单小云.细胞凋亡的分子医学.北京:军事医学出版社,2002:273-289.
  • 3李崇剑,高润霖,杨跃进,陈纪林.易损斑块的病理生理机制及其检测的研究进展[J].中华心血管病杂志,2004,32(6):570-573. 被引量:88
  • 4Davies JR,Rudd JH,Weissberg PL.Molecular and metabolic imaging of atherosclerosis.J Nucl Med,2004,45 (11):1898-1907.
  • 5Qin G,Zhang Y,Cao W,et al.Molecular imaging of atherosclerotic plaques with technetium-99m-labelled antisense oligonucleotides.Eur J Nucl Med Mol Imaging,2005,32 (1):6-14.
  • 6Lederman RJ,Raylman RR,Fisher SJ,et al.Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG).Nucl Med Commun,2001,22 (7):747-753.
  • 7Kolodgie FD,Narula J,Haider N,et al.Apoptosis in atherosclerosis.Does it contribute to plaque instability? Cardiology Clinics,2001,19(1):127-139.
  • 8Kolodgie FD,Petrov A,Virmari R,et al.Targeting of apoptotic macrophages and experimental atheroma with radiolabeled Annexin Ⅴ:a technique with potential for noninvasive imaging of vulnerable plaque.Circulation,2003,108(25):3134-3139.
  • 9Kietselaer BL,Reutelingsperger CP,Heidendal GA,et al.Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotid-artery atherosclerosis.N Engl J Med,2004,350(14):1472-1473.
  • 10Johnson LL,Schofield L,Donahay T,et al.99mTc-Annexin Ⅴ imaging for in vivo detection of atherosclerotic lesion in porcine coronary arteries.J Nucl Med,2005,46(7):1186-1193.

二级参考文献25

  • 1Brose N, Petrenko A G, Sudhof T C, et al. Synaptotagmin: a calcium sensor on the synaptic vesicle surface. Science, 1992, 256(5059): 1021~1025
  • 2Matthew W D, Tsavaler L, Reichardt L F. Identification of a synaptic vesicle-specific protein with a wide tissue distribution in neuronal and neurosecretory tissue. J Cell Biol, 1981, 91(1): 257~269
  • 3Fernandez-Chacon R, Konigstorfer A, Gerber S H, et al. Synaptotagmin Ⅰ functions as a calcium regulator of release probability. Nature, 2001, 410(6824): 41~49
  • 4Südhof T C. Synaptotagmins: why so many? J Biol Cell, 2002, 277(10): 7629-7632
  • 5Sutton R B, Davletov B A, Berghuis A M, et al. Structure of the first C2 domain of synaptotagmin Ⅰ: a novel Ca2+/phospholipid binding fold. Cell, 1995, 80(6): 929~938
  • 6Demel R A. Monolayers-description of use and interaction. Method Enzymol, 1974, 32(part B): 539~545
  • 7Han X H, Sui S F, Yang F Y. A mini-trough for the study of membrane insertion ability of proteins. Thin Solid Films, 1996, 284/285(1):789~792
  • 8Mi L Z, Wang H W, Sui S F. Interaction of rabbit C-reactive protein with phospholipid monolayers studied by microfluorescence film balance with an externally applied electric field. Biophysical J, 1997,73(1): 446~451
  • 9Demel R A, London Y, Geurts van Kessel W S M, et al. The specific interaction of myelin basic protein with lipids at the air-water interface. Biochim Biophys Acta, 1973, 311(4): 507~519
  • 10Demel R A, Geurts van Kessel W S, Zwaal R F, et al. Relation between various phospholipase actions on human red cell membranes and the interfacial phospholipid pressure in monolayers. Bichim Biophys Acta, 1975, 406(1): 97~107

共引文献92

同被引文献126

引证文献6

二级引证文献14

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部