Abstract
Background: A signaling pathway of the small GTPase Rho and Rho-associated coiledcoil- forming protein kinase (ROCK), regulates the contraction of endothelial cells. We studied the effects of Y-27632, a specific ROCK inhibitor, to clarify the role of Rho/ROCK in the pathogenesis of ischemia-reperfusion lung injury in a rat model of single-lung transplantation (LTX).
Methods: We flushed 5 donor rat lungs with Euro-Collins solution, and 5 donor lungs with Euro-Collins + Y-27632, 0.03 mg/ml, and preserved the lungs for 6 h at 4°C before reperfusion for 4 h. The 5 rat recipients of Y-27632-treated lungs also received a 10-mg/kg bolus of Y-27632 i.p. 30 min before reperfusion.
Results: Pretreatment of the donor lungs and recipient rats with Y-27632 prominently suppressed the post-LTX edema, while the permeability index was only slightly decreased. The (1. numbers of neutrophils and macrophages, and (2. tumor necrosis factor (TNF)-α concentration, were significantly lower in the bronchoalveolar lavage fluid of treated than untreated lungs.
Conclusions: Y-27632 (1. inhibited the migration of inflammatory cells into the alveolar space, (2. decreased the production of TNF-α, and (3. attenuated the edema after LTX. Endothelial Rho and ROCK may play an important role in the pathogenesis of post-LTX injury.
Original language | English |
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Pages (from-to) | 359-364 |
Number of pages | 6 |
Journal | Annals of Thoracic and Cardiovascular Surgery |
Volume | 20 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2014 Jan 1 |
Keywords
- Ischemia reperfusion injury
- Lung transplantation
- Rat model
- Rho/Rho-associated coiled-coil-forming protein kinase
- Tumor necrosis factor-α
ASJC Scopus subject areas
- Surgery
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine
- Gastroenterology