Targeted and thrombolytic effect of urokinase-loaded immunoliposomes on acute pulmonary embolism in rabbits / 中国病理生理杂志

ABSTRACT

AIM: To prepare urokinase-loaded immunoliposomes, with anti-D-dimer mouse monoclonal antibody that can selectively target to thrombotic site and test the thrombolytic effect in the rabbit model of acute pulmonary embolism (PE) in early phase. METHODS: 40 New Zealand white rabbits were randomly divided into five groups TBS group (TBS buffer, negative control group), urokinase (UK) group (150 000 IU/kg UK, positive control group), Lip group (Lip-UK, containing 50 000 IU/kg UK), Ab group (Ab-Lip-UK, containing 50 000 IU/kg UK) and 2 Ab group (2 Ab-Lip-UK, containing 50 000 IU/kg UK but double DDmAb of Ab group). PE model was established. Five minutes later, five solutions (TBS, UK, Lip-UK, Ab-Lip-UK, 2 Ab-Lip-UK) were transfused through femoral vein respectively. Right ventricular systolic pressure (RVSP) and right ventricular diastolic pressure (RVDP) were estimated within one hour. The pathological changes of lung, heart, liver and kidney were all observed. RESULTS: RVSP in TBS group had no significant changes within one hour after administration. However, RVSP had respective notable decline at 30 min, 40 min, 30 min, 20 min in UK, Lip, Ab and 2 Ab group, respectively. The means of residual emboli were as follows 4.0±0 in TBS group, 2.4±0.9 in UK group, 3.1±0.6 in Lip group, 2.4±0.9 in Ab group and 1.9±0.6 in 2 Ab group. The lungs in each group showed scattering local congestion, effusion and swelling on the surface. Obvious hemorrhage of heart, kidney and liver was found with HE staining in UK group, no pathologic change was observed in other groups. CONCLUSION: 2 Ab-Lip-UK with early thrombolytic effect and security may be an ideal thrombolytic agent for treating pulmonary embolism.