四川大学学报（医学版）2012，Vol.43Issue(3)：451-457,7.
诊断超声介导自制微泡造影剂联合尿激酶体外溶栓效应及参数优化的实验研究
Effect of Diagnostic Ultrasound-mediated Microbubble Contrast and Urokinase on Augmentation Thrombolysis and Optimization of the Major Parameters: an in vitro Study
摘要
Abstract
Objective To investigate the efficacy of diagnostic ultrasound and microbubble contrast C MB) on enhancing thrombolysis in combination with urokinase (UK) and to determine the optimal combination for thrombolysis in vitro. Methods Four types of standardized red thrombus were prepared in vitro, including 3-hour-old(3 h), 6-hour-old(6 h). 12 hour-old(12 h). and 24-hour-old(24 h). The major parameters for the designed experiments included transmit powers of ultrasound (factor A, 5%, 25%, 50%, 100%), MB volumes (factor B, 50 μL, 100 μL, 200 μL, 400 μL), UK concentrations (factor C, 100 U/mL. 200 U/mL, 400 U/mL, 800 U/mL), and lysis time (factor D, 10 min, 20 min, 30 min, 40 min). An orthogonal array experimental design (OAD) based on four levels L16(45) of the above four parameters was employed to optimize the thrombolysis conditions. During the procedure of thrombolysis, the diagnostic ultrasound frequency was fixed at 1. 82 MHz. The histopathological changes measured by HE staining and scanning electron microscope (SEM) were carried out to observe the clots before and after thrombolysis. The loss of clot weight before and after treatment was measured to determine the lysis efficiency (LE). Analysis of variance (ANOVA) was performed to assess the LE according to the L16(45) matrix. Results The HE staining and SEM observation of thrombolysis under the following experimental conditions of 5% ultrasound transmit power, 400 μL MB volume, 800 U/mL UK concentration, and 40 min lysis time showed remarkable disaggregation of fibrin nets. The above four factors had significant impact on thrombus (all P<0. 05), among which UK concentrations (factor C) was the most significant one. The optimal scheme was determined as a C4-D4-A1-B4 mode, with UK concentration 800 U/mL, lysis time 40 min, transmit power 5%, and MB volume 400 μL, respectively. The LE curves for 3h clots were superior to the others. The lysis efficiencies for the clots showed significant differences among different type of thrombus (all P<0. 05). Conclusion 1. 82 MHz diagnostic ultrasound and microbubble contrast can be applied to augment thrombolysis in vitro even with a transmit power as low as 5%. Under the condition of fixed ultrasound frequency, the LE of thrombus increase with increased UK concentrations, lysis time and MB volumes, and decrease with increased thrombus ages.关键词
诊断超声/微泡造影剂/尿激酶/体外溶栓/栓龄/参数优化Key words
Diagnostic ultrasound/ Microbubble contrast/ Urokinase/ Thrombus age Thrombolysis in vitro/ Optimization引用本文复制引用
喻琴梅,王红,孟文彤,李艳秋,杨金荣,李军,周翔,牛挺..诊断超声介导自制微泡造影剂联合尿激酶体外溶栓效应及参数优化的实验研究[J].四川大学学报（医学版）,2012,43(3):451-457,7.基金项目
国家自然科学基金(批准号30970839)和四川省科技厅-应用基础(批准号2010JY0006)资助 （批准号30970839）
