Huang Liang-Ti, Lin Chien-Huang, Chou Hsiu-Chu, Chen Chung-Ming
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan ; Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, No. 111, Section 3, Hsing-Long Road, Taipei 116, Taiwan.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan.
Biomed Res Int. 2014;2014:749097. doi: 10.1155/2014/749097. Epub 2014 Jun 12.
Ventilator-induced lung injury-(VILI-) induced endothelial permeability is regulated through the Rho-dependent signaling pathway. Ibuprofen inhibits Rho activation in animal models of spinal-cord injury and Alzheimer's disease. The study aims to investigate ibuprofen effects on high tidal volume associated VILI.
Twenty-eight adult male Sprague-Dawley rats were randomized to receive a ventilation strategy with three different interventions for 2 h: (1) a high-volume zero-positive end-expiratory pressure (PEEP) (HVZP) group; (2) an HVZP + ibuprofen 15 mg/kg group; and (3) an HVZP + ibuprofen 30 mg/kg group. A fourth group without ventilation served as the control group. Rho-kinase activity was determined by ratio of phosphorylated ezrin, radixin, and moesin (p-ERM), substrates of Rho-kinase, to total ERM. VILI was characterized by increased pulmonary protein leak, wet-to-dry weight ratio, cytokines level, and Rho guanine nucleotide exchange factor (GEF-H1), RhoA activity, p-ERM/total ERM, and p-myosin light chain (MLC) protein expression.
Ibuprofen pretreatment significantly reduced the HVZP ventilation-induced increase in pulmonary protein leak, wet-to-dry weight ratio, bronchoalveolar lavage fluid interleukin-6 and RANTES levels, and lung GEF-H1, RhoA activity, p-ERM/total ERM, and p-MLC protein expression.
Ibuprofen attenuated high tidal volume induced pulmonary endothelial hyperpermeability. This protective effect was associated with a reduced Rho-kinase activity.
呼吸机诱导性肺损伤（VILI）所致的内皮通透性是通过Rho依赖性信号通路调控的。布洛芬在脊髓损伤和阿尔茨海默病动物模型中可抑制Rho激活。本研究旨在探讨布洛芬对高潮气量相关VILI的影响。
28只成年雄性Sprague-Dawley大鼠被随机分为三组，接受三种不同干预措施的通气策略2小时：（1）高潮气量零呼气末正压（PEEP）（HVZP）组；（2）HVZP + 15 mg/kg布洛芬组；（3）HVZP + 30 mg/kg布洛芬组。第四组不进行通气作为对照组。通过磷酸化埃兹蛋白、根蛋白和膜突蛋白（p-ERM）（Rho激酶的底物）与总ERM的比值来测定Rho激酶活性。VILI的特征为肺蛋白渗漏增加、湿干重比增加、细胞因子水平升高以及Rho鸟嘌呤核苷酸交换因子（GEF-H1）、RhoA活性、p-ERM/总ERM和磷酸化肌球蛋白轻链（MLC）蛋白表达增加。
布洛芬预处理显著降低了HVZP通气诱导的肺蛋白渗漏增加、湿干重比增加、支气管肺泡灌洗液白细胞介素-6和RANTES水平升高，以及肺GEF-H1、RhoA活性、p-ERM/总ERM和p-MLC蛋白表达增加。
布洛芬减轻了高潮气量诱导的肺内皮高通透性。这种保护作用与Rho激酶活性降低有关。
