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丙泊酚预处理通过激活磷酸肌醇-3-激酶/蛋白激酶B通路减轻脂多糖诱导的大鼠急性肺损伤。

Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway.

作者信息

Zhao L L, Hu G C, Zhu S S, Li J F, Liu G J

机构信息

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.

出版信息

Braz J Med Biol Res. 2014 Dec;47(12):1062-7. doi: 10.1590/1414-431X20143949. Epub 2014 Oct 14.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fecc/4244672/80f2e8122cca/1414-431X-bjmbr-47-12-01062-gf001.jpg

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