Wang Bing, Wang Li, Zhou Xiao-Bo, Liu Ya-Min, Wang Mei, Qin Hao, Wang Chong-Bao, Liu Ju, Yu Xiao-Jiang, Zang Wei-Jin
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, PR China.
Thromb Haemost. 2008 Aug;100(2):356-61.
Clot-targeted microbubbles (TMB) were developed based on oligopeptide specific to the glycoprotein IIb/IIIa receptor on active platelets. In this study, we aimed to elucidate the thrombolysis effect of this TMB in both intraarterial and intravenous application and compare the clot lysis efficiency of the TMB and untargeted microbubbles(UTMB) in presence of external low frequency ultrasound (LFUS) (800 kHz, 2.4 w/cm(2), pulse-wave). An acute arterial occlusion model was induced in rabbits by blocking the common carotid artery with an autogenous clot. Animals were randomized to five groups to receive the following treatment: 1) intra-arterial TMB and LFUS (IA TMB/LFUS); 2) intravenous TMB and LFUS (IV TMB/LFUS); 3) intravenous untargeted-microbubbles and LFUS (IV UTMB/LFUS); 4) LFUS only; 5) intra-arterial normal saline (NS) control. Declotting score and a variation of thrombolysis-in-myocardial-infarction (TIMI) flow scale were applied to assess clot clearance and flow restore according to the angiogram. IA TMB/LFUS treatment produced highest declotting score (3.5 +/- 0.53) and success rate (100%). IV TMB/LFUS treatment produced a higher declotting score (1.95 +/- 1.12) than LFUS treatment (0.53 +/- 0.38) (P = 0.026). and higher TIMI (1.94 +/- 0.62 vs. 0.47 +/- 0.44, P = 0.020). When administrated intravenously, TMB/LFUS created a higher declotting score (1.95 +/- 1.12) than that of UTMB/LFUS (0.61 +/- 0.43) (P = 0.033). The superiority was observed in TIMI also (1.94 +/- 0.62 vs. 0.72 +/- 0.25, P = 0.041). The results demonstrate that either intra-arterial or intravenous TMB is effective in clearing clot in-vivo model. The TMB showed advantage over UTMB in systemic administration.
基于活性血小板上糖蛋白IIb/IIIa受体特异性寡肽开发了靶向血栓的微泡（TMB）。在本研究中，我们旨在阐明这种TMB在动脉内和静脉内应用中的溶栓效果，并比较在外部低频超声（LFUS）（800kHz，2.4w/cm²，脉冲波）存在下TMB和非靶向微泡（UTMB）的血栓溶解效率。通过用自体血栓阻塞兔颈总动脉诱导急性动脉闭塞模型。将动物随机分为五组接受以下治疗：1）动脉内TMB和LFUS（IA TMB/LFUS）；2）静脉内TMB和LFUS（IV TMB/LFUS）；3）静脉内非靶向微泡和LFUS（IV UTMB/LFUS）；4）仅LFUS；5）动脉内生理盐水（NS）对照。根据血管造影应用去凝评分和心肌梗死溶栓（TIMI）血流分级变化来评估血栓清除和血流恢复情况。IA TMB/LFUS治疗产生最高去凝评分（3.5±0.53）和成功率（100%）。IV TMB/LFUS治疗产生的去凝评分（1.95±1.12）高于LFUS治疗（0.53±0.38）（P=0.026），TIMI评分也更高（1.94±0.62对0.47±0.44，P=0.020）。静脉给药时，TMB/LFUS产生的去凝评分（1.95±1.12）高于UTMB/LFUS（0.61±0.43）（P=0.033）。在TIMI评分中也观察到优势（1.94±0.62对0.72±0.25，P=0.041）。结果表明，动脉内或静脉内TMB在体内模型中清除血栓均有效。在全身给药中，TMB显示出优于UTMB的优势。
