Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-kappa B pathway

摘要

The purpose of this study was to investigate the protective effect of PD against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its potential mechanism. In vivo, PD and dexamethasone were intraperitoneally administered 1 h before LPS stimulation. Then, mice were sacrificed at 6 h post-LPS stimulation. Neutrophil number, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) in bronchoalveolar lavage fluid (BALF) were determined, as well as lung wet to dry ratio (W/D) and polymorphonuclear (MPO) activity. The protein expressions of Toll like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), IL-1R-associated kinases I (IRAK1), IRAK4, inhibitor of nuclear factor kappa-B kinase (IKK)alpha, p-IKK alpha, IKK beta, p-IKK beta, inhibitor of NF-kappa B (I kappa B alpha), p-I kappa B alpha and NF-kappa B in lung tissues were assessed. Besides, we detected the IL-6, IL-1 beta, IL-8, TNF-alpha levels and TLR4, MyD88, NF-kappa B protein expressions in LPS-induced BEAS-2B cells. Consequently, PD significantly inhibited the levels of W/D, MPO, neutrophils number, TNF-alpha, IL-6, IL-113 and reversed TLR4-MyD88-NF-kappa B signaling pathway in lung tissues. In vitro assays, PD effectively negatively mediated the inflammatory cytokines and ameliorated the high expressions of TLR4, MyD88, NF-kappa B caused by LPS simulation in Human bronchial epithelial BEAS-2B cells. This study indicated that PD played a protective role in LPS-induced ALI and BEAS-2B cells. The results supported further study of PD as potential candidate for acute lung injury. (C) 2015 Elsevier B.V. All rights reserved.