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血栓性疾病是临床常见疾病,涉及全身各脏器,其发生与血管损伤、血液成分变化及局部血流淤滞等改变有关。P-选择素作为血小板/内皮细胞活化标志及黏附受体,参与血栓形成起始过程,并是连接炎症与血栓的重要介质和靶分子。为此,进行了以P-选择素为靶标的分子磁共振成像(magnetic resonance imaging,MRI)在血栓早期诊断中的应用研究。利用自制的抗P-选择素单抗(PsL-EGFmAb),制备了具有P-选择素靶特异性的MR对比剂(Gd-DTPA)n-BSA-PsL-EGFmAb,并在体外MR成像基础上,进行了犬静脉血栓模型活体观察。结果显示,该对比剂可明显增强体外模拟血小板血栓和全血血栓的显像信号。进一步发现,相应于P-选择素在建模后即刻犬受损静脉血管内膜及形成的血栓部位表达,模型犬在损伤局部注射对比剂后30min,MR成像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,显示了与P-选择素表达一致的信号强化效果。另从股静脉损伤部位的远心端注射对比剂后30min至1h,也显示上述成像效果,2h至4h血栓信号强度由明显上升渐见趋缓,延迟24h信号强度减弱。此外,该对比剂对实验犬的生命体征及心、肺、肝、肾等理化指标均无明显影响。研究结果提示,研制的MR对比剂对P-选择素具有靶向特异性,可活体内早期定位显像及反映血栓形成状态,且对机体重要脏器功能无影响,这为早期诊断血栓性疾病提供了一种可行的方法。
Thrombotic diseases are common clinical diseases, involving the various organs of the body, its occurrence and vascular injury, blood composition changes and changes in local blood stasis and other changes. P-selectin, as a platelet / endothelial activation marker and adhesion receptor, is involved in the initiation of thrombosis and is an important mediator and target of inflammation and thrombus. To this end, P-selectin-targeted molecular magnetic resonance imaging (magnetic resonance imaging, MRI) in the early diagnosis of thrombosis in the application. The MR contrast agent (Gd-DTPA) n-BSA-PsL-EGFmAb with P-selectin target specificity was prepared by home-made anti-P-selectin monoclonal antibody (PsL-EGFmAb) , In vivo observation of dog venous thrombosis model. The results show that the contrast agent can significantly enhance in vitro simulation of platelet thrombosis and thrombosis signal imaging. It was further found that corresponding to the expression of P-selectin in the venous intima and the thrombus formed in the canine immediately after modeling, the MR imaging of the model dog showed a higher blood vessel than that of the surrounding muscle at 30 min after the local injection of the contrast agent Signal, 1h can be seen mural thrombogenic signal to 3h with thrombosis increased and continued to strengthen, showing the same signal enhancement with P-selectin expression. Another from the distal femoral venous injury site injection of contrast agent 30min to 1h, also showed the above imaging results, 2h to 4h thrombosis signal intensity gradually slowed down, delayed signal intensity decreased 24h. In addition, the contrast agent on the experimental dog’s vital signs and heart, lung, liver, kidney and other physical and chemical indicators had no significant effect. The results suggest that the developed MR contrast agent targeting specificity of P-selectin, early localization and imaging in vivo can reflect the status of thrombosis, and has no effect on the function of vital organs, which is an early diagnosis of thrombotic diseases Provides a viable approach.