尿激酶免疫脂质体对肺栓塞家兔的靶向溶栓治疗作用  

Targeted and thrombolytic effect of urokinase-loaded immunoliposomes on acute pulmonary embolism in rabbits

作　　者：滕孝静[1] 刘瑜[2] 周以健[2] 董小黎[2] 

机构地区：[1]首都医科大学附属北京友谊医院病理科,北京100050 [2]首都医科大学基础医学院病理教研室,北京100069

出　　处：《中国病理生理杂志》2009年第12期2408-2412,共5页Chinese Journal of Pathophysiology

基　　金：北京市教育委员会科技发展计划面上资助项目(No.KM200710025006)

摘　　要：目的:以鼠抗人纤维蛋白D-二聚体单克隆抗体(DDmAb)为靶向装置,制备尿激酶(UK)的血栓靶向脂质体即尿激酶免疫脂质体,并在兔急性肺动脉栓塞模型上观察其早期溶栓效果。方法:新西兰大白兔40只,随机分为5组:TBS组(TBS缓冲液,阴性对照组)、UK组(15×104IU/kgUK,阳性对照组)、Lip组(5×104IU/kgUK的Lip-UK)、Ab组(5×104IU/kgUK的Ab-Lip-UK)和2Ab组(5×104IU/kgUK但DDmAb用量为Ab组2倍,2Ab-Lip-UK)。各组成功建立急性肺动脉栓塞模型后,分别以TBS缓冲液、UK、Lip-UK、Ab-Lip-UK和2Ab-Lip-UK各30mL经股静脉输入,进行兔体内溶栓实验,并观察右心室收缩压(RVSP)和右心室舒张压(RVDP)在1h内随时间变化的情况。实验结束后,处死动物并取材,观察肺动脉内残留栓子数及心、肝、肾的肉眼和组织学变化。结果:TBS组RVSP在溶栓后1h内无显著变化,UK组、Lip组、Ab组、2Ab组RVSP分别于溶栓后30min、40min、30min、20min后显著下降。TBS组、UK组、Lip组、Ab组、2Ab组肺内残留栓子数分别为:(4.0±0,2.4±0.9,3.1±0.6,2.4±0.9,1.9±0.6)个。各组肺均有不同程度的淤血、水肿表现。HE染色除UK组心、肝、肾有出血外,其余组未见出血。结论:以2Ab-Lip-UK这种具有双重靶向作用的药物进行溶栓治疗是肺动脉栓塞的一种理想溶栓方式,可缩短有效溶栓时间,疗效好且安全。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 ali 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 grouo, no oathologic 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.

关 键 词：尿激酶免疫脂质体 肺栓塞 靶向治疗 

分 类 号：R563.5[医药卫生—呼吸系统]