Attenuation of Lung Ischemia-Reperfusion Injury by Rho-Associated Kinase Inhibition in a Rat Model of Lung Transplantation

作者：Kohno Mitsutomo^*; Watanabe Masazumi; Goto Taichiro; Kamiyama Ikuo; Ohtsuka Takashi; Tasaka Sadatomo; Sawafuji Makoto

来源：Annals of Thoracic and Cardiovascular Surgery, 2014, 20(5): 359-364.

DOI：10.5761/atcs.oa.13-00095

• ischemia reperfusion injury
• lung transplantation
• rat model
• tumor necrosis factor-alpha
• Rho/Rho-associated coiled-coil-forming protein kinase

Background: A signaling pathway of the small GTPase Rho and Rho-associated coiled-coil-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 degrees 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)-alpha 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-alpha, and (3) attenuated the edema after LTX. Endothelial Rho and ROCK may play an important role in the pathogenesis of post-LTX injury.

• 出版日期2014