Kohno Mitsutomo, Watanabe Masazumi, Goto Taichiro, Kamiyama Ikuo, Ohtsuka Takashi, Tasaka Sadatomo, Sawafuji Makoto
Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Ann Thorac Cardiovasc Surg. 2014;20(5):359-64. doi: 10.5761/atcs.oa.13-00095. Epub 2013 Oct 3.
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).
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.
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.
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.
小GTP酶Rho和Rho相关卷曲螺旋形成蛋白激酶（ROCK）的信号通路调节内皮细胞的收缩。我们研究了特异性ROCK抑制剂Y-27632的作用，以阐明Rho/ROCK在单肺移植（LTX）大鼠模型缺血再灌注肺损伤发病机制中的作用。
我们用Euro-Collins溶液冲洗5只供体大鼠肺，用含0.03 mg/ml Y-27632的Euro-Collins溶液冲洗另外5只供体肺，在4°C下保存6小时后再灌注4小时。接受Y-27632处理肺的5只大鼠受体在再灌注前30分钟还腹腔注射10 mg/kg的Y-27632。
用Y-27632预处理供体肺和受体大鼠可显著抑制LTX后的水肿，而通透性指数仅略有下降。处理组肺的支气管肺泡灌洗液中（1）中性粒细胞和巨噬细胞数量以及（2）肿瘤坏死因子（TNF）-α浓度明显低于未处理组。
Y-27632（1）抑制炎症细胞向肺泡腔的迁移，（2）降低TNF-α的产生，（3）减轻LTX后的水肿。内皮Rho和ROCK可能在LTX后损伤的发病机制中起重要作用。
