携尿激酶靶向微泡联合超声在体溶栓后尿激酶浓度的实验研究  

Experimental study of urokinase concentration after in vivo thrombolysis with urokinase targeting microbubbles combined with ultrasound

作　　者：关丽娜[1] 杨灵洁[1] 王春梅[1] 南晶 穆玉明[1] Guan Lina;Yang Lingjie;Wang Chunmei;Nan Jing;Mu Yuming(Department of Cardiac Ultrasound Diagnosis,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学第一附属医院心脏超声诊断科,乌鲁木齐830011

出　　处：《中华超声影像学杂志》2021年第4期336-340,共5页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金(30860267)。

摘　　要：目的制备携尿激酶靶向血栓微泡联合低频超声溶解兔股动脉内血栓,通过尿激酶浓度的变化探讨其可能的溶栓机制。方法24只股动脉闭塞性血栓模型兔分为4组,每组6只:①尿激酶静脉注射(UK)组;②诊断超声+非靶向微泡+尿激酶静脉注射(US+M+UK)组;③血栓靶向微泡携尿激酶(R+UK)组;④诊断超声+血栓靶向微泡携带尿激酶(US+R+UK)组。诊断超声照射30 min,后监测0 min、10 min、20 min、30 min、60 min、90 min和120 min血流量,同时监测尿激酶浓度变化,对血流量及尿激酶浓度变化特点进行分析。结果120 min后UK、US+M+UK组血流量未实现再通,R+UK组实现部分再通,US+R+UK组完全再通(P<0.001)。与基础状态比较,R+UK组和R+UK+US组均在60 min时出现降低,差异有统计学意义(P<0.05)。结论靶向微泡携带尿激酶可以使血栓局部的尿激酶浓度达到最高,而超声及靶向微泡的联合作用可以促进尿激酶进入血栓内部,最终实现最佳的溶栓效果。Objective To prepare urokinase targeted thrombus microbubbles combined with low frequency ultrasound to dissolve thrombus in rabbit femoral artery,and to explore the mechanism of thrombolysis through the change of urokinase concentration.Methods Twenty-four rabbits with thrombosed femoral artery were randomly divided into four treatment groups:urokinase alone(UK)group,ultrasound with non-targeted microbubble and urokinase(US+M+UK)group,platelet-targeted microbubble with urokinase(R+UK)group,ultrasound with platelet-targeted microbubble and urokinase(US+R+UK)group.Thrombus-targeted microbubbles were injected through the ear vein and irradiated by ultrasound for 30 minutes,and the pulsed Doppler blood flow meter was used to continuously monitor the blood flow at 0 min,10 min,20 min,30 min,60 min,90 min and 120 min after injection.At the same time,the changes in urokinase concentration were monitored,and the characteristics of blood flow and urokinase concentration changes were analyzed.Results UK and US+M+UK groups failed to show recanalization at 120 minutes after treatment.In contrast,the US+R+UK and R+UK groups both achieved persistent recanalization(P<0.001).Compared with the basal state.Both the R+UK group and R+UK+US group showed a decrease at 60 minutes,and the difference was statistically significant(P<0.05).Conclusions In the thrombolysis process of low-frequency ultrasound combined with a targeted contrast agent carrying urokinase,the targeting can make the local urokinase concentration of thrombus reach the highest level.At the same time,ultrasound and targeted microbubbles promote urokinase to enter the thrombus,and finally achieve the strongest thrombolytic effect.

关 键 词：超声处理 尿激酶浓度 血流量 溶栓 

分 类 号：R965[医药卫生—药理学]