P选择素在肾病综合征并发深静脉血栓中的作用及犬血栓模型磁共振分子成像观察  

Effect of P-selectin on deep vein thrombosis in nephrotic syndrome and molecular magnetic resonance imaging targeting P-selectin in a dog model of venous thrombosis

作　　者：周同[1] 李晓[1] 赵亚鹏[1] 金佩佩[4] 王学锋[4] 钟高仁[5] 汪登斌[2] 张明钧[3] 陈楠[1] 王鸿利[4] 

机构地区：[1]上海交通大学医学院附属瑞金医院肾脏科,200025 [2]上海交通大学医学院附属瑞金医院放射科,200025 [3]上海交通大学医学院附属瑞金医院动物实验室,200025 [4]上海血液学研究所血栓与止血研究室 [5]复旦大学放射药学研究所

出　　处：《中华肾脏病杂志》2008年第12期883-889,共7页Chinese Journal of Nephrology

基　　金：基金项目：国家自然科学基金（39970340,30570865）;上海市科委基础研究重点项目（05JC14039）;上海交通大学医学院科技创业基金（JYCJ0503）

摘　　要：目的观察P选择素在肾病综合征（NS）并发深静脉血栓形成（DVT）中作用，探讨P选择素靶向对比剂及分子磁共振成像（MRI）在DVT犬模型早期诊断应用的可行性。方法（1）选择我院2005年至2006年间住院NS患者41例，根据核素深静脉造影检查有无伴发DVT，再分为DVT组和无DVT组，检测患者血中P选择素含量。（2）选择健康成年毕格犬，建立DVT模型，并按造模即刻、1h、3h采血并取静脉损伤节段，行血管组织和血中P选择素含量检测。（3）利用研制的抗P选择素单抗，制成P选择素靶向对比剂，结合体外犬静脉损伤节段血管MRI，进行犬活体内观察。结果（1）NS患者血P选择素水平较健康组显著增高（P〈O．01），DVT组又较无伴DVT组明显增高（P〈0．01）。（2）模型犬血P选择素水平较对照犬显著增高（P〈0．05），且于受损血管内膜及血栓形成部位明显表达。（3）制备的MRI对比剂，体外可明显增强犬离体受损血管与血栓部位显像信号。体内于犬静脉损伤局部注射对比剂30min，MRI即显示高于周围肌肉显影的血管信号；1h可见附壁血栓增强信号；至3h随血栓形成增大而持续强化，实验组对比度噪声比（CNR）值与对照组比较，差异有统计学意义（11．51±2．32比2．71±O．86，P〈0．01），且显示了与P选择素表达一致的信号强化效果。另从犬损伤部位远心端注射对比剂30rain至1h，也显示了上述成像效果；2h至4h血栓信号由明显上升渐见趋缓，延迟24h信号强度减弱，实验组CNR值与对照组间差异也有统计学意义（10．40±2．15比1．93±0．57，P〈0．01）。此外，该对比剂对实验犬的生命体征及心、肺、肝、肾等脏器均无明显影响。结论P选择素参与NS合并DVT。利用P选择素单抗MRI对比剂，可在活体内早期定位显像及反映血栓形成状态，为DVT早期诊断提供了一种可行方法。Objectives To detect the effects of P-selectin on deep venous thrombosis （DVT） in nephrotic syndrome （NS）, and to evaluate the molecular magnetic resonance imaging （MRI） with a P-selectin targeted contrast agent in diagnosis of thrombosis in the early phase.Methods （1） Forty-one patients with NS hospitalized in our department from 2005 to 2006 were enrolled in this study. They were assigned into DVT group and non-DVT group according to lower limbs radionuclide imaging （RNV） with ~Tc MAA. Blood P-selectin level was measured by ELISA method. （2） P-seleetin was detected both in injured vein and blood immediately, 1 h and 3 h after the dog DVT model was established. （3） The P-selectin-targeted contrast agent was developed by conjugating anti-P-selectin lectin-EGF domain monoclonal antibody （PsL-EGFmAb） which was prepared by our lab. The potential of this contrast agent used in vitro molecular imaging experiment as well as in vivo experiment in dog DVT model was investigated. Results （1） Blood P- selectin level was elevated in patients with NS. It was much higher in DVT group than that in non- DVT group. （2） Blood P-selectin level was also elevated in DVT dogs and P-selectin expressed immediately in tunica intima of injured vein and subsequently in thrombus after the model established. （3） Mural thrombus showed higher signal visualization than surrounding muscle in 30 rain after contrast agent injection. These enhanced signals exhibited P-selectin specificity and persisted from the initiation of intima lesions to 3 h after development of thrombosis. There was significant Differences in contrast-to-noise ratio （CNR） of the experiment group and the control group （11.50±2.32 vs 2.71±0.86, P〈0.01）. The same results were derived from 30 min to 1 h after contrast agent being injected in distal to heart part of the injured vessel, and the signal decreased 24 h later. Differences in CNR of the experiment group and the control group were also statistically significant （

关 键 词：肾病综合征 静脉血栓形成 早期诊断 磁共振成像 P选择素 

分 类 号：R692.3[医药卫生—泌尿科学] R445.2[医药卫生—外科学]