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[血栓靶向尿激酶免疫脂质体对兔肺栓塞的溶栓作用]

[Thrombolysis of rabbit's pulmonary embolism with thrombus-targeted urokinase immune liposome].

作者信息

Lü Cui-Ping, Yang Hui, Wang Jue, Dong Xiao-Li

机构信息

Histology and Embryology Department of North China Coal Medical University, Tangshan 063000, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Nov;37(11):1035-8.

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Acute PE could be successfully treated by the thrombus-targeted urokinase immune liposome with D-dimer monoclonal antibody.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

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