摘要
目的探讨采用携Sialyl Lewisx多聚体(PSLex)微泡靶向CEUS评价动脉系统血管炎症反应的可行性。方法构建分别携P-Sialyl Lewisx(MB-S)、抗P-选择素单抗(MB-P)和同型对照单抗(MB-C)的3种微泡,应用流式细胞仪分析其配体结合率,利用平行板流动腔和Image-Pro Plus图像分析软件,分析3种微泡在0.5、2.0和4.0dyn/cm2剪切应力下的靶向结合数目。对急性腹主动脉炎症模型(炎症组)和假手术模型(对照组)小鼠各9只,采用弹丸式注入以上微泡,6min后行CEUS检查,测量腹主动脉显影的声强度(VI)。结果 MB-P、MB-S的配体结合率比较差异无统计学意义(P>0.05)。在3种剪切应力下,MB-S和MB-P的全程(6min)结合数目均高于MB-C(P均<0.05);在0.5dyn/cm2时,MB-S的全程结合数目与MB-P的差异无统计学意义(P>0.05),而在2.0和4.0dyn/cm2时,MB-S的全程结合数目明显多于MB-P(P均<0.05);各种微泡的全程结合数目均随剪切应力提高而减少(P均<0.05)。在炎症组中,MB-S、MB-P和MB-C的VI值依次降低(P均<0.05);除MB-C外,MB-S和MB-P在炎症组的VI值均分别高于对照组(P均<0.05)。结论在高剪切应力下MB-S的结合能力明显优于MB-P,可用于评价动脉血管内皮炎症反应。
Objective To approach the feasibility of targeted CEUS with microbubbles bearing polymeric Sialyl Lewis x for evaluation of mouse abdominal aorta inflammation.Methods Selectin-targeted（with polymeric sialyl Lewis x or anti-P-selectin monoclonal antibodies） microbubbles（MB-S,MB-P） and isotype control microbubbles（with isotype control monoclonal antibodies） microbubbles（MB-C） were prepared by attaching the ligands to lipid-microbubbles.The binding rate of ligands in microbubbles was measured by quantitative flow cytometry.A parallel plate flow chamber was used to observe the firmly adherent numbers of microbubbles at 3different shear stress（0.5,2.0and 4.0dyn/cm 2） over 6min.The mice were divided into acute abdominal aorta inflammatory model（inflammatory group,n=9） and sham surgery model（control group,n=9）,and then microbubbles were injected randomly and respectively via a catheter placed in the tail vein.The video intensity（VI） was observed at 6min after microbubbles bolus injection.Results The ligand-binding rates of microbubbles were not significantly different between MB-S and MB-P（P〈0.05）.At the same shear stress,adhesive numbers of MB-S and MB-P at 6min were much more than those of MB-C（both P〈0.05）.At 0.5dyn/cm 2 shear stress,there was no significant difference between the adhesive numbers of MB-S and MB-P（P〈0.05）,while at 2.0and 4.0dyn/cm 2,bindings of MB-S to the targets were obviously greater than those of MB-P（both P〈0.05）.In all flow conditions,the adhesive numbers of microbubbles to the targets decreased as the shear flow increased.In the inflammatory group,VI of microbubbles decreased from MB-S to MB-C（all P〈0.05）,and except MB-C,VI of MB-S and MB-P was higher than that of control group（both P〈0.05）.Conclusion In high shear stress,MB-S has greater binding capability than MB-P,which may be used to evaluate the inflammation response in arterial vessels.
出处
《中国介入影像与治疗学》
CSCD
2012年第4期295-299,共5页
Chinese Journal of Interventional Imaging and Therapy
基金
国家自然科学基金(30870722)
广东省自然基金团队项目(S2011030003134)
