Department of Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil.
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Ilha do Fundão, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Respir Physiol Neurobiol. 2014 Feb 1;192:134-46. doi: 10.1016/j.resp.2013.12.012. Epub 2013 Dec 26.
We evaluated whether Rho-kinase inhibition (Y-27632) modulated distal lung responsiveness, inflammation, extracellular matrix remodeling and oxidative stress activation in guinea pigs (GPs) with chronic allergic inflammation. GPs were submitted to inhalation of ovalbumin (OVA-2×/week/4 weeks). From the 5th inhalation on, the Rho-kinase inhibitor group animals were submitted to Y-27632 inhalation 10min before each inhalation of OVA. Seventy-two hours after the seventh inhalation, the oscillatory mechanics of the distal lung strips were assessed under the baseline condition and after the ovalbumin challenge. Subsequently, the lung slices were submitted to morphometry. Rho-kinase inhibition in the ovalbumin-exposed animals attenuated distal lung elastance and resistance, eosinophils, IL-2, IL-4, IL-5, IL-13, TIMP-1, MMP-9, TGF-β, IFN-γ, NF-κB and iNOS-positive cells and the volume fraction of 8-iso-PGF2α, elastic, collagen and actin in alveolar walls compared with the OVA group (P<0.05). Rho-kinase inhibition contributed to the control of distal lung responsiveness, eosinophilic and Th1/Th2 responses and extracellular matrix remodeling in an animal model of chronic allergic inflammation.
我们评估了 Rho 激酶抑制（Y-27632）是否调节了慢性变应性炎症豚鼠（GPs）的远端肺反应性、炎症、细胞外基质重塑和氧化应激激活。GPs 接受卵清蛋白（OVA）吸入（2×/周/4 周）。从第五次吸入开始，Rho 激酶抑制剂组动物在每次 OVA 吸入前 10 分钟接受 Y-27632 吸入。第七次吸入后 72 小时，在基础状态和卵清蛋白挑战后评估远端肺条的振荡力学。随后，将肺切片进行形态测量。与 OVA 组相比，卵清蛋白暴露动物中的 Rho 激酶抑制降低了远端肺弹性和阻力、嗜酸性粒细胞、IL-2、IL-4、IL-5、IL-13、TIMP-1、MMP-9、TGF-β、IFN-γ、NF-κB 和 iNOS 阳性细胞以及肺泡壁中 8-iso-PGF2α、弹性、胶原和肌动蛋白的体积分数（P<0.05）。Rho 激酶抑制有助于控制慢性变应性炎症动物模型中的远端肺反应性、嗜酸性粒细胞和 Th1/Th2 反应以及细胞外基质重塑。
