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.
ABSTRACT
Objective In order to investigate the mechanism of the remodeling of pulmonary vascular in hypoxic pulmonary hypertension,normobaric hypoxic rat model (FIO 2=10%)was used to observe the changes of fibronectin(FN)and leminin(LN)within the pulmonary artery by morphological methods. Methods The normobaric hypoxic chamber was used to establish the hypoxic rat model. The lungs were taken off and stained with immunohistochemical method.Some specimens were examined by electromicroscopy. Results Immunohistochemical analysis revealed progressive increase in the deposition of FN and LN,which was most prominent in hypoxia 7d group.The content of FN was higher than LN.Electromicroscope revealed that the SMC of tunia media had transitted from a contractile to a synthetic phenotype. Conclusion Long term hypoxic exposure resulted in increasing of FN and LN in the wall of pulmonary artery.These increase not only raise the tension and make thickening of the vessels themselves,but also provide an environment for the transition of SMC from a contractile to a synthetic phenotype.FN and LN played an important role in the remodeling of pulmonary vascular directly and indirectly. [