Effect of dexmedetomidine on HMGB1/TLRs signaling pathway during lung injury in septic rats

Abstract

Objective To evaluate the effect of dexmedetomidine on high-mobility group box 1 protein (HMGB1)/Toll-like receptors (TLRs) signaling pathway during lung injury in septic rats. Methods Twenty-four SPF healthy adult male Wistar rats, aged 15-18 weeks, weighing 200-250 g, were divided into 3 groups (n=8 each) using a random number table: sham operation group (group S), sepsis group (group Sep) and dexmedetomidine group (group D). Dexmedetomidine 25 μg/kg was intraperitoneally injected in D group, while the equal volume of normal saline was given instead in S and Sep groups.Sepsis was produced by cecal ligation and puncture in Sep and D groups.The rats were sacrificed at 24 h after operation, and the right lung was removed for examination of the pathological changes which were scored and for determination of myeloperoxidase (MPO) activity, content of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in lung tissues (by enzyme-linked immunosorbent assay), wet to dry weight ratio (W/D ratio) and expression of HMGB1, TLR2 and TLR4 in lung tissues (by Western blot). Results Compared with group S, the MPO activity, lung injury score, W/D ratio, content of IL-1β, IL-6, TNF-α and expression of HMGB1, TLR2 and TLR4 were significantly increased in Sep and D groups (P<0.05). Compared with group Sep, the MPO activity, lung injury score, W/D ratio, content of IL-1β, IL-6, TNF-α and expression of HMGB1, TLR2 and TLR4 were significantly decreased in group D (P<0.05). Conclusion Dexmedetomidine reduces lung injury through inhibiting HMGB1/TLRs signaling pathway in septic rats. Key words: Dexmedetomidine; Sepsis; Respiratory distress syndrome, adult; High mobility group proteins; Toll-like receptors