Lü Cui-Ping, Yang Hui, Wang Jue, Dong Xiao-Li
Histology and Embryology Department of North China Coal Medical University, Tangshan 063000, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Nov;37(11):1035-8.
To develop thrombus-targeted urokinase immune liposome through incorporating D-dimer monoclonal antibody (DDmAb) to liposome and observe the thrombolytic efficiency in a rabbit pulmonary thromboembolism (PE) model.
Reverse-phase evaporation method was used to develop targeted urokinase immune liposome by coupling DDmAb to urokinase liposome (liposomal-encapsulated urokinase) with glutaraldehyde. The PE models were induced by injecting 4 autologous emboli (2 mm x 5 mm) through jugular vein catheter into pulmonary arteries. New Zealand white rabbits (n = 32) were randomized into four groups: A group (TBS), B group (150 000 IU/kg UK), C group (30 000 IU/kg urokinase liposome) and D group (30 000 IU/kg urokinase immune liposome). The right ventricular pressure and the emboli size in pulmonary arteries were determined.
The right ventricular pressure increased significantly in PE rabbits (P < 0.01), the average value is (6.75 +/- 6.82) mm Hg (1 mm Hg = 0.133 kPa). Eighty minutes post various treatments, right ventricular pressure remained unchanged as post PE in group A [(40.15 +/- 11.22) mm Hg vs. (41.67 +/- 14.23) mm Hg], decreased to baseline level in group B and D [(34.71 +/- 8.67) mm Hg vs. (33.98 +/- 9.32) mm Hg, (30.65 +/- 6.67) mm Hg vs. (30.77 +/- 6.85) mm Hg, all P > 0.05], decreased but not returned to normal value in group C. Residual emboli size remained unchanged in group A and partly reduced in group C and more significantly reduced in group B and D. Hemorrhage of heart, kidney and liver was evidenced in group A but not in other groups.
Acute PE could be successfully treated by the thrombus-targeted urokinase immune liposome with D-dimer monoclonal antibody.
通过将D - 二聚体单克隆抗体（DDmAb）掺入脂质体来制备血栓靶向尿激酶免疫脂质体，并观察其在兔肺血栓栓塞症（PE）模型中的溶栓效果。
采用反相蒸发法，通过戊二醛将DDmAb偶联至尿激酶脂质体（脂质体包裹的尿激酶）来制备靶向尿激酶免疫脂质体。通过颈静脉导管向肺动脉注射4个自体栓子（2 mm×5 mm）诱导建立PE模型。将32只新西兰白兔随机分为四组：A组（TBS）、B组（150 000 IU/kg尿激酶）、C组（30 000 IU/kg尿激酶脂质体）和D组（30 000 IU/kg尿激酶免疫脂质体）。测定右心室压力和肺动脉内栓子大小。
PE兔右心室压力显著升高（P < 0.01），平均值为（6.75±6.82）mmHg（1 mmHg = 0.133 kPa）。各种治疗后80分钟，A组右心室压力与PE后无变化[（40.15±11.22）mmHg对（41.67±14.23）mmHg]，B组和D组降至基线水平[（34.71±8.67）mmHg对（33.98±9.32）mmHg，（30.65±6.67）mmHg对（30.77±6.85）mmHg，均P > 0.05]，C组降低但未恢复至正常水平。A组残余栓子大小无变化，C组部分减小，B组和D组减小更显著。A组出现心脏、肾脏和肝脏出血，其他组未出现。
含D - 二聚体单克隆抗体的血栓靶向尿激酶免疫脂质体可成功治疗急性PE。
