Journal of Thrombosis and Thrombolysis

, Volume 37, Issue 3, pp 303–309 | Cite as

The ultrasound contrast imaging properties of lipid microbubbles loaded with urokinase in dog livers and their thrombolytic effects when combined with low-frequency ultrasound in vitro

  • Shu-Ting Ren
  • Xiao-Ning Kang
  • Yi-Ran Liao
  • Wei Wang
  • Hong Ai
  • Li-Na Chen
  • Hui-Ting Luo
  • Rong-Guo Fu
  • Li-Fang Tan
  • Xin-Liang Shen
  • Bing WangEmail author


A new microbubble loaded with urokinase (uPA-MB) was explored in a previous study. However, its zeta potential and ultrasound contrast imaging properties and its thrombolytic effects when combined with low-frequency ultrasound (LFUS) were unclear. The zeta potential and ultrasound contrast imaging property of 5 uPA-MBs loading with 50,000 IU uPA was respectively detected using a Malvern laser particle analyzer and a Logiq 9 digital premium ultrasound system. Its ultrasound contrast imaging property was performed on the livers of two healthy dogs to compare with SonoVue. And the clot mass loss rate, D-dimer concentration and surface morphology of the clot residues were measured to evaluate the thrombolytic effect after treatment with three doses of 5 uPA-MBs combined with LFUS in vitro. The zeta potential of 5 uPA-MBs (−27.0 ± 2.40 mV) was higher than that of normal microbubbles (−36.95 ± 1.77 mV). Contrast-enhanced imaging of the hepatic vessels using 5 uPA-MBs was similar to SonoVue, while the imaging duration of 5 uPA-MBs (10 min) was longer than SonoVue (6 min). The thrombolytic effect of three doses of uPA-MBs combined with LFUS was significantly better than that of the control group and showed dose dependence. The 5 uPA-MBs have a negative charge on their surface and good echogenicity as ultrasound contrast agents. The 5 uPA-MBs combined with LFUS can promote thrombolysis in a dose-dependent manner.


Microbubble Ultrasound contrast imaging Urokinase Thrombolysis 



The authors would like to thank Hua-Sheng Liu, Shao-Li Cheng, and Jiang-Wei Liang for help in the experiment. The present study was supported by the Scientific Technology Planning Foundation of Shaanxi Province (No. 2010K12-01), the National 863 Plan (No. 2010AA022907), the National Natural Science Foundation (General Program, No. 30872410), Province Ministry Graveness Engineering Program (Nos. 2009ZDKG-20, 2008ZDKG-60, 2007ZDKG-290) and Xi’an Jiaotong University Project (Nos. 2009xjtujc14 and 2009xjtujc26).

Conflict of interest

All authors declare that there are no financial or personal relationships that might lead to conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shu-Ting Ren
    • 1
    • 2
  • Xiao-Ning Kang
    • 1
    • 2
    • 3
  • Yi-Ran Liao
    • 2
    • 4
  • Wei Wang
    • 2
    • 5
  • Hong Ai
    • 6
  • Li-Na Chen
    • 2
    • 4
  • Hui-Ting Luo
    • 7
  • Rong-Guo Fu
    • 8
  • Li-Fang Tan
    • 6
  • Xin-Liang Shen
    • 9
  • Bing Wang
    • 1
    • 2
    Email author
  1. 1.Department of Pathology, School of MedicineXi’an Jiaotong UniversityXi’anChina
  2. 2.Therapeutic Vaccines Engineering Center of Shaanxi ProvinceXi’anChina
  3. 3.Elementary Department 2 of Shaanxi Energy InstituteXi’anChina
  4. 4.Department of Pharmacology, School of MedicineXi’an Jiaotong UniversityXi’anChina
  5. 5.Clinical Laboratory, First Affiliated Hospital of Medical CollegeXi’an Jiaotong UniversityXi’anChina
  6. 6.Department of Ultrasound Imaging, First Affiliated Hospital of Medical CollegeXi’an Jiaotong UniversityXi’anChina
  7. 7.Department of Ultrasound ImagingAffiliated Hospital of Shaanxi University of Chinese MedicineXianyangChina
  8. 8.Department of Nephrology, Second Affiliated Hospital of Medical CollegeXi’an Jiaotong UniversityXi’anChina
  9. 9.China National Biotechnology GroupBeijingChina

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