BQ-123对兔急性肺栓塞溶栓后缺血-再灌注损伤的保护作用

Protective effects of endothelin-1 receptor antagonist （BQ-123） against lung ischemia-reperfusion injury on the model of acute pulmonary embolism in rabbits

目的观察内皮素-1（ET-1）受体拮抗剂BQ-123对兔急性肺栓塞溶栓后肺缺血-再灌注损伤的保护作用。方法日本大耳白兔24只，雌雄不限，体质量（3．0±0．5）b，随机分成4组（每组6只）即：假手术组（SHAM组）、栓塞组（PE组）、尿激酶组（UK组）、尿激酶＋BQ-123组（UK＋BQ组）。各组分别于栓塞前、栓塞后0．5、2、4h监测记录肺动脉平均压并采静脉血检测血浆ET-1浓度，实验结束后测肺组织的湿／干比值（W／D比值）、超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量变化。结果栓塞后0．5h，PE组、UK组、UK＋BQ组肺动脉平均压分别为（19．01±0．60）mmHg（1mmHg=0．133kPa）、（20．14±0．85）mmHg、（19．79±0．78）mmHg与SHAM组（18．92±0．63）mm Hg比较肺动脉平均压升高（P〈0．05）；UK＋BQ组（310．77±30．58）ng／L较UK组（371．18±35．43）ng／L在栓塞后4h血浆ET-1浓度下降（P〈0．05）；UK＋BQ组与UK组比较，W／D比值、肺组织MDA含量降低，SOD活性升高（P〈0．05）。结论急性肺栓塞溶栓后早期出现了肺缺血再灌注损伤，ET-1可能是导致损伤的主要因素；急性肺栓塞溶栓前给予ET-1受体拮抗剂BQ-123对急性肺栓塞溶栓后缺血-再灌注损伤有一定的保护作用。

Objective To explore the protective effects of endothelin-1 （ ET-1 ） receptor antagonist BQ-123 against ischemia-reperfusion injury after thrombolysis in acute pulmonary embolism. Methods Twenty-four big-ear Japanese rabbits （ no limit of male or female） were divided into 4 groups randomly （n = 6 in each group） ： sham group （sham-operated group）, PE group （pulmonary embolism group）, UK group （thrombolysis group）, BQ group （UK ＋ BQ-123 group）. We detected the levels of ET-1 in the venous blood plasma and mean pulmonary arterial pressure （MPAP） before and 0. 5, 2, 4 h after embolization. The ratio of lung tissue wet/dry （W/D）, the superoxide dismutase （SOD） activity and malondialdehyde （MDA） content at the end of the experiment were measured. Results As compared with sham group [ （ 18.92 ± 0. 63） mm Hg（ 1 mm Hg = 0. 133 kPa） ], the MPAP in PE group （ 19. 01 ± 0. 60） mm Hg, UK group （20. 14 ± 0. 85） mm Hg, and BQ group （ 19. 79 ± 0. 78） mm Hg was increased significantly at 0. 5 h after embolization （ P 〈 0.05 ）. There was no significant difference in MPAP between BQ group and UK group at 2 h and 4 h after embolization. The levels of plasma ET-1 in BQ group were reduced more significantly than UK group at 4 h after embolization. As compared with sham group, the W/D and MDA content were increased, but SOD activity was reduced in PE group and UK group at the end of the experiment, and the same results were obtained between UK group and PE group （P 〈 0. 05 ）. The W/D ratio and MDA content were lower, and SOD activity was higher in BQ group than in UK group （ P 〈0. 05）. Conclusion Lung ischemi- a-reperfusion injury appeared in thrombolysis after acute pulmonary embolism, and BQ-123 may exert the antagonistic effets.