Effect of sevoflurane preconditioning on HMGB1/TLR4/NF-κB signaling pathway during lung ischemia-reperfusion in rats

Abstract

Objective To evaluate the effect of sevoflurane preconditioning on high-mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway during lung ischemia-reperfusion(I/R)in rats. Methods Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 3 groups (n=12 each) using a random number table method: sham operation group (group S), lung I/R group (group I/R) and sevoflurane preconditioning group (group SP). The right pulmonary hilum was only isolated but not ligated in group S. Lung I/R was induced by clamping the right pulmonary hilum for 60 min followed by 120 min of reperfusion in anesthetized rats in group I/R.In group SP, 2.1% sevoflurane was inhaled for 30 min to perform sevoflurane preconditioning, and the lung I/R model was established at 10 min after the end of inhalation.The rats were sacrificed at 120 min of reperfusion, and the lungs were removed for examination of the pathological changes which were scored and for determination of wet to dry weight ratio (W/D ratio), content of tumor necrosis factor-alpha (TNF-α) in lung tissues (by enzyme-linked immunosorbent assay) and expression of HMGB1, TLR4 and NF-κB protein in lung tissues (by Western blot). Results Compared with group S, the pathological scores, W/D ratio and content of TNF-α were significantly increased, and the expression of HMGB1, TLR4 and NF-κB was up-regulated in I/R and SP groups (P<0.05). Compared with group I/R, the pathological scores, W/D ratio and content of TNF-α were significantly decreased, and the expression of HMGB1, TLR4 and NF-κB was down-regulated (P<0.05), and the pathological changes of lung tissues were significantly attenuated in group SP. Conclusion Sevoflurane preconditioning reduces lung I/R injury probably through inhibiting HMGB1/TLR4/NF-κB signaling pathway in rats. Key words: Anesthetics, inhalation; Lung; Reperfusion injury; High mobility group proteins; Toll-like receptors; NF-kappaB