摘要
目的制备RGDS/rt-PA双负载靶向微泡,分析其对富血小板血栓(PRT)的靶向性和溶栓效果。方法制备不同剂量梯度的RGDS及rt-PA单负载靶向微泡,以其最佳结合剂量、按照不同加入顺序(先加入RGDS,再加入rt-PA;先加入rt-PA,再加入RGDS;将RGDS及rt-PA混匀后加入)分别制备RGDS/rt-PA双负载靶向微泡,检测其结合率。比较裸微泡、单负载及双负载微泡的物理特性(直径、浓度及pH值),不同剂量梯度的同一配体与微泡的单负载结合率,同一剂量梯度的不同配体与微泡的单负载结合率,加入顺序不同的配体与微泡的双负载结合率。制备体外PRT模型,检测RGDS/rt-PA双负载靶向微泡的声学显像特征、靶向溶栓能力。结果不同微泡间的物理特性差异均无统计学意义(P均>0.05)。不同剂量梯度的rt-PA、RGDS与微泡单负载结合率的差异均有统计学意义,同一剂量梯度的rt-PA与微泡单负载的结合率均低于RGDS(P均<0.05)。加入顺序不同的配体与微泡的双负载结合率的差异有统计学意义(F=16.090,P=0.004)。将RGDS/rt-PA双负载靶向微泡注入血栓模型管腔后,超声可见均匀分布的点状高回声,血栓边界回声明显增强;扫描电镜下可见纤维蛋白网状结构明显破坏、纤维束断裂成细沙状,并可见变形融合的血细胞。结论 RGDS/rt-PA双负载靶向微泡性质稳定,与配体的结合率高,声学显像特征好,具备一定的PRT靶向性及溶栓能力。
Objective To construct co-carrying RGDS and rt-PA targeted microbubbles,and to analyze their targeting and thrombolytic effects on platelet-rich thrombus（PRT）.Methods RGDS and rt-PA single loaded microbubbles were prepared with different dosage gradient,respectively.The co-carrying RGDS/rt-PA target microbubbles were prepared by the optimum single loaded combination rate in different adding orders（first added RGDS,then added rt-PA;first added rtPA,then added RGDS;added RGDS and rt-PA simultaneously）,and the co-carrying binding rate was observed,respectively.The physical properties of bare microbubbles,single loaded and double loaded microbubbles（diameter,concentration and pH value）were compared.The binding rate of the same single ligand with microbubbles at different dosage gradient,the binding rate of different ligands with microbubbles at the same dosage gradient,as well as the binding rate of co-carrying microbubbles with different adding order were compared.Finally,the acoustic imaging and targeted thrombolysis of co-carrying RGDS/rt-PA microbubbles by preparing the model of PRT in vitro were detected.ResultsThere was no significant difference of physical characteristics among different microbubbles（all P〉0.05）.The binding rate of the same single ligand with microbubbles at different dosage gradient were significantly different,and the binding rate of rt-PA with microbubble was lower than that of RGDS at the same dosage gradient（P〈0.05）.The binding rate of co-carrying microbubbles with different adding orders were significantly different（F=16.090,P 〈0.004）.In vitro thrombi models,the co-carrying RGDS/rt-PA microbubbles showed high-echo dots with uniform distribution,and the echo of the thrombi boundary enhanced obviously.The electron microscopy showed the fibrin structure was significantly damaged,the fiber bundles were broken into fine sand,and the deformed and fused blood cells were visible.ConclusionRGDS/rt-PA microbubbles have stable properties,high binding rate with ligands,great acoustic development,as well as fine PRT targeting and thrombolytic ability.
作者
王晓妤
穆玉明
麦培培
史琪
狄敏
黄伟良
关丽娜
WANG Xiaoyu;MU Yuming;MAI Peipei;SHI Qi;DI Min;HUANG Weiliang;GUAN Li’na(Department of Echocardiography,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)
出处
《中国医学影像技术》
CSCD
北大核心
2018年第8期1126-1130,共5页
Chinese Journal of Medical Imaging Technology
基金
新疆维吾尔自治区自然科学基金青年基金(2017D01C353)
新疆医科大学研究生创新创业项目(CXCY2017036)
新疆研究生科研创新项目(XJGRI2017080)
关键词
超声检查
靶向微泡
血栓溶解疗法
Ultrasonography
Targeted microbubbles
Thrombolytic therapy
