title: Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression.
abstract: We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1β levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.
authors.affiliation: Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, China. maling27@hotmail.com
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Wu
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Zhang
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
authors.forename: Akinori
authors.initials: A
authors.lastname: Uchiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Mashimo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Fujino
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D015742:Propofol / Q000627:therapeutic use*; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D015742:Propofol