Tissue plasminogen activator attenuates ventilator-induced lung injury in rats  

作　　者：Liang-ti HUANG Hsiu-chu CHOU Leng-fang WANG Chung-ming CHEN 

机构地区：[1]Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, China [2]Department of Pediat-rics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, China [3]Department of Anatomy [4]Department of Biochemistry,School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, China [5]Department of Pediatrics, Taipei MedicalUniversity Hospital, Taipei, Taiwan, China [6]Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical Univer-sity, Taipei, Taiwan, China

出　　处：《Acta Pharmacologica Sinica》2012年第8期991-997,共7页中国药理学报（英文版）

摘　　要：Aim： To test the hypothesis that the tissue plasminogen activator （tPA） may counteract the inhibitory effect of plasminogen activator inhibitors （PAl） and attenuate lung injury in a rat model of ventilator-induced lung injury （VILI）. Methods： Adult male Sprague-Dawley rats were ventilated with a HVZP （high-volume zero PEEP） protocol for 2 h at a tidal volume of 30 mL/kg, a respiratory rate of 25 breaths/min, and an inspired oxygen fraction of 21%, The rats were divided into 3 groups （n=7 for each）： HVZP＋tPA group receiving tPA （1.25 mg/kg, iv） 15 rain before ventilation, HVZP group receiving HVZP＋vehicle injection, and a control group receiving no ventilation. After 2 h of ventilation, the rats were killed; blood and lungs were collected for biochemical and histological analyses. Results＇ HVZP ventilation significantly increased total protein content and the concentration of macrophage inflammatory protein-2 （MIP-2） in the bronchoalveolar lavage fluid （BALF） as well as the lung injury score. Rats that received HVZP ventilation had significantly higher lung PAl-1 mRNA expression, plasma PAl-1 and plasma D-dimer levels than the control animals, tPA treatment significantly reduced the BALF total protein and the lung injury score as compared to the HVZP group, tPA treatment also significantly decreased the plasma D-dimer levels and the HVZP ventilation-induced lung vascular fibrin thrombi, tPA treatment showed no effect on MIP-2 level in BALE Conclusion： These results demonstrate that VILI increases lung PAl-1 mRNA expression, plasma levels of PAl-1 and D-dimers, lung injury score and vascular fibrin deposition, tPA can attenuate VILI by decreasing capillary-alveolar protein leakage as well as local and systemic coagulation as shown by decreased lung vascular fibrin deposition and plasma D-dimers.Aim： To test the hypothesis that the tissue plasminogen activator （tPA） may counteract the inhibitory effect of plasminogen activator inhibitors （PAl） and attenuate lung injury in a rat model of ventilator-induced lung injury （VILI）. Methods： Adult male Sprague-Dawley rats were ventilated with a HVZP （high-volume zero PEEP） protocol for 2 h at a tidal volume of 30 mL/kg, a respiratory rate of 25 breaths/min, and an inspired oxygen fraction of 21%, The rats were divided into 3 groups （n=7 for each）： HVZP＋tPA group receiving tPA （1.25 mg/kg, iv） 15 rain before ventilation, HVZP group receiving HVZP＋vehicle injection, and a control group receiving no ventilation. After 2 h of ventilation, the rats were killed; blood and lungs were collected for biochemical and histological analyses. Results＇ HVZP ventilation significantly increased total protein content and the concentration of macrophage inflammatory protein-2 （MIP-2） in the bronchoalveolar lavage fluid （BALF） as well as the lung injury score. Rats that received HVZP ventilation had significantly higher lung PAl-1 mRNA expression, plasma PAl-1 and plasma D-dimer levels than the control animals, tPA treatment significantly reduced the BALF total protein and the lung injury score as compared to the HVZP group, tPA treatment also significantly decreased the plasma D-dimer levels and the HVZP ventilation-induced lung vascular fibrin thrombi, tPA treatment showed no effect on MIP-2 level in BALE Conclusion： These results demonstrate that VILI increases lung PAl-1 mRNA expression, plasma levels of PAl-1 and D-dimers, lung injury score and vascular fibrin deposition, tPA can attenuate VILI by decreasing capillary-alveolar protein leakage as well as local and systemic coagulation as shown by decreased lung vascular fibrin deposition and plasma D-dimers.

关 键 词：tissue plasminogen activator （tPA） ventilator-induced lung injury （VILI） plasminogen activator inhibitor-1 （PAl-l） mac-rophage inflammatory protein-2 （MIP-2） D-DIMER FIBRIN bronchoalveolar lavage fluid （BALF） 

分 类 号：Q949.753.5[生物学—植物学] X503.1[环境科学与工程—环境工程]