Effects of preconditioning with different concentrations of sevoflurane on the expression of Toll-like receptor 4 in rats with acute lung injury induced by lipopolysaccharide

Abstract

Objective To investigate the effects of preconditioning with different concentrations of sevoflurane on the expression of Toll-like receptor 4 (TLR4) in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS).Methods Thirty adult male Sprague-Dawlcy rats,wcighing 200-250 g,were randomly divided into 5 groups (n =6 each):normal saline group (group NS),group ALI,and preconditioning with different concentrations of sevoflurane groups (groups S1-3).ALI was induced by intratracheal instillation of LPS 5 mg/kg.Groups S1-3 inhaled 1.2％,2.4 ％ and 4.8 ％ sevoflurane for 30 min respectively,and ALI was induced 30 min later.The rats were sacrificed at 12 h after administration of LPS or normal saline and lungs were removed for microscopic examination and for determination of TLR4 mRNA and protein expression in lung tissues and concentrations of TNF-α and IL-1β in broncho-alveolar lavage fluid (BALF).W/D lung weight ratio was calculated.Results Compared with group NS,W/D lung weight ratio and concentrations of TNF-a and IL-1β in BALF were significantly increased and the expression of TLR4 mRNA and protein was up-regulated in groups ALI and S1-3 (P ＜ 0.01).Compared with group ALI,the parameters mentioned above were significantly decreased in groups S2 and S3,and the concentrations of TNF-α and IL-1 β in BALF were significantly decreased and the expression of TLR4 mRNA was down-regulated in group S1 (P ＜ 0.05 or 0.01).The parameters mentioned above were significantly lower in groups S2 and S3 than in group S1 (P ＜ 0.05).The pathologic changes were significantly attenuated in groups S1-3 compared with group ALI.Conclusion Preconditioning with sevoflurane can concentration-dependently reduce LPS-induced ALI in rats through inhibiting the up-regulation of TLR4 expression in lung tissues and reducing the inflammatory response. Key words: Anesthetics, inhalation; Respiratory distress syndrome, adult; Toll-like receptors 4; Preconditioning