靶向微泡、尿激酶溶栓后预防微循环再栓塞的实验研究

Recent studies were showed that no matter what kind of thrombolysis methods chould be released the thrombosis material after thrombolysis, and lead to microcirculation embolism. Our previous National Natural Science Fund Project ( project number: 30860267 ), the results showed that, application of diagnostic ultrasound combined with targeted microbubble carrying urokinase dissolves the femoral artery thrombosis, but also found that, in the implementation of targeted intravascular thrombosis effective solution, branch of small vessels and its end there have been varying degrees of occlusion, consider the possible reason for dissolving thrombus, fragment is too large, resulting in microcirculation embolism. Therefore, how to make complete thrombolysis and prevent microthrombosis after thrombolysis formation, leading to embolism occurred in thrombolytic therapy has the important clinical significance The purpose of this study is, based on preliminary experimental study has been carried out in the animal production in vivo, femoral artery thrombosis, targeted microbubble contrast agent after intravenous injection of urokinase thrombolytic drugs will carry, the factors of thrombus size after thrombolysis, firing frequency, ultrasonic intensity, time, thrombolytic drug dose and other factors, to analyze, to not only to the target completely dissolve thrombus, and achieve the best experimental methods and prevention of embolism microcirculation

近来研究发现，无论何种溶栓方式，溶栓后均有致血栓物质的再释放，造成微循环再栓塞。我们既往的 国家自然科学基金项目（项目编号：30860267），的研究结果显示，应用诊断超声联合靶向微泡携带尿激酶完全溶解了股动脉内血栓，但同时也发现，在实现了靶向血管内的血栓有效溶解后，其末端的分支小血管继而出现了不同程度的再闭塞，考虑其可能的原因，为血栓的溶解片段过大，进而导致微循环栓塞。因此，如何使血栓完全溶解并防止溶栓后的微血栓形成，导致再栓塞发生在溶栓治疗中具有重要的临床意义。 本研究的目的在于，在已开展的前期实验研究的基础上，制作活体动物股动脉内血栓，将携带溶栓药物尿激酶的靶向微泡造影剂经静脉注射后，将影响溶栓后血栓大小的因素，超声的发射频率、强度、时间，溶栓药物的剂量等因素，进行分层分析后，达到不仅对靶向血管内血栓的完全溶解，同时达到预防微循环的再栓塞的最佳实验方法。

如何使血栓完全溶解并防止溶栓后的微血栓形成，导致再栓塞发生在溶栓治疗中具有重要的临床意义。研究提示低频诊断超声联合携尿激酶的靶向微泡造影剂对兔股动脉血栓有溶解效应，如何能对靶向血管内血栓达到完全溶解，同时达到预防微循环的再栓塞，对临床治疗更有价值。该研究项目通过制作新西兰大白兔单侧股动脉血栓模型，将微泡造影剂静脉注入兔体内，联合超声照射对血栓溶栓治疗。选用析因设计表对不同超声频率、不同尿激酶剂量、不同超声照射时间的实验组合，进行股动脉血栓体内溶栓实验。研究结果提示通过适当调整超声相关参数，能进一步减少药物剂量，减少超声照射时问、减少药物的副作用发生，使溶栓治疗更加安全有效。实验研究显示，将局部低频诊断超声照射+靶向微泡+溶栓药物尿激酶的三者联合应用，对股动脉血栓溶栓有效。超声照射频率为2.2MHz、尿激酶剂量为1.5mg/Kg可获得最好的溶栓效果，实现了血管的完全溶通，并且未见微循环再栓塞；应用30 min或60 min的超声照射时间对溶栓效果无显著影响。