Zhao L L, Hu G C, Zhu S S, Li J F, Liu G J
Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
Braz J Med Biol Res. 2014 Dec;47(12):1062-7. doi: 10.1590/1414-431X20143949. Epub 2014 Oct 14.
The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway.
本研究旨在探讨丙泊酚预处理对脂多糖(LPS)诱导的急性肺损伤(ALI)的影响以及磷酸肌醇-3-激酶/蛋白激酶B(PI3K/Akt)信号通路在此过程中的作用。在注射LPS后48小时测定生存率。在LPS攻击后1小时,检测肺组织湿干重比,并使用二辛可宁酸法或酶联免疫吸附测定法(ELISA)测定支气管肺泡灌洗液(BALF)中蛋白质、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的浓度。通过肺组织学检查评估肺损伤。采用蛋白质免疫印迹法检测肺组织中PI3K和p-Akt的表达水平。丙泊酚预处理可延长LPS攻击大鼠的生存时间,降低BALF中蛋白质、TNF-α和IL-6的浓度,减轻ALI,并增加肺组织中PI3K和p-Akt的表达,而PI3K/Akt信号通路特异性抑制剂渥曼青霉素则可减弱这种作用。我们的研究表明,丙泊酚预处理可减轻LPS诱导的ALI,部分是通过激活PI3K/Akt信号通路实现的。