• Jing Liu, Xinhua Huang, Siping Hu, Huanzhong He, and Zhipeng Meng.
• Department of anesthesia, Huzhou maternal & child health care hospital, wuxing area NO.2 East Street, Huzhou City, 313000 Zhejiang province, China. Electronic address: liujing-1229@163.com.
• Biomed. Pharmacother. 2019 Oct 1; 118: 109314.

ObjectiveToll-like receptor 4(TLR-4)/nuclear factor-kappa B(NF-κB) pathway plays an important role in inducing acute lung injury (ALI). Studies have proved Dexmedetomidine (Dex) inhibits inflammatory response to mitigate lipopolysaccharide (LPS)-induced ALI and protect against multiorgan injury in various scenarios via restraining TLR-4/NF-κB signaling pathway. Many of the known downstream molecules have been orientated with a protein caveolin-1(Cav-1), which is supposed to take part in regulating TLR4-mediated inflammatory responses. However, its mechanisms have not been confirmed. The aim of this study is to evaluate the protective effects and potential mechanisms of Dex against LPS-induced ALI in male rats.MethodsMale rats received tail-vein injection of LPS to form ALI model. Rats were administrated with intraperitoneal injection Dex0.5 h before ALI. At 6 h after LPS injection, bronchoalveolar lavage fluid (BALF) and lung tissue were harvested. We stained the lung tissue sections with hematoxylin eosin (HE) staining to observe the histopathological damage and measure the ALI pathology score. We also measured the wet-to-dry(W/D) weight ratio of lung tissue. Lung myeloperoxidase (MPO) and inflammatory cytokines in the BALF were detected by Enzyme-linked immunosorbent assay(ELISA). Protein levels of Cav-1, TLR-4 and NF-κB in lung tissue were tested by immunohistochemistry method. The mRNA expression of Cav-1, TLR4 and the NF-κB in lung tissue were measured to determine the related mechanisms by quantitative real-time polymerase chain reaction(RT-PCR).ResultsIt was indicated that Dex pretreatment markedly mitigated pathomorphologic changes and pathological lung injury scores. Besides, Dex pretreatment obviously decreased the W/D weight ratio of lung tissue, attenuated MPO activity significantly, along with LPS-stimulated augment of lung inflammatory cells infiltration in BALF. Moreover, compared with LPS model group, Dex pretreatment apparently increased the protein levels of Cav-1 downregulated by sepsis and decreased the protein levels of TLR-4 and NF-κB in lung tissue. Furthermore, Dex pretreatment apparently upregulated the expression of Cav-1 mRNA, restrained TLR4 and NF-κB mRNA.ConclusionDex pretreatment protects against LPS-induced ALI via inhibiting the activation of the TLR-4/NF-kB signaling pathway by upregulating the expression of Cav-1 downregulated by sepsis.Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

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