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3-Methyladenine and dexmedetomidine reverse lipopolysaccharide-induced acute lung injury through the inhibition of inflammation and autophagy

  • Authors:
    • Dengfeng Ding
    • Shiyuan Xu
    • Hongfei Zhang
    • Wei Zhao
    • Xueping Zhang
    • Yuanxu Jiang
    • Ping Wang
    • Zhongliang Dai
    • Junzhi Zhang

  • View Affiliations

  • Published online on: February 2, 2018     https://doi.org/10.3892/etm.2018.5832
  • Pages: 3516-3522
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Abstract

The aim of the present study was to investigate the effects of 3-methyladenine (3-MA) and dexmedetomidine (DEX) pretreatment on lipopolysaccharide (LPS)‑induced acute lung injury (ALI) and the potential mechanism underlying the effects. LPS was instilled into the trachea of BALB/c mice to induce the ALI model. Solutions of 3‑MA or DEX were intravenously injected into the mice 1 h later to establish the 3‑MA and DEX groups. On days 1, 3 and 5 after the injections, arterial blood gas analysis was conducted, and the lung wet‑dry weight ratio (W/D) was determined. In addition, albumin, cytokine and myeloperoxidase (MPO) contents were evaluated using ELISAs, and hematoxylin and eosin (H&E) staining was conducted. Furthermore, western blot analysis was used to evaluate the protein expression levels of microtubule‑associated protein 1A/1B‑light chain 3 (LC3)‑I, LC3‑II, autophagy protein 5 (ATG5), Rab7 and lysosome‑associated membrane protein 1 (LAMP1), and reverse transcription quantitative polymerase chain reaction (RT‑qPCR) was used to detect the mRNA expression levels of nuclear factor‑κB (NF‑κB) and Toll‑like receptor 4 (TLR4). Treatment with 3‑MA or DEX increased the blood partial pressure of oxygen level compared with that in the model group, and restored the W/D and blood partial pressure of carbon dioxide to normal levels. The content of tumor necrosis factor‑α, interleukin‑6 and albumin in bronchoalveolar fluid and MPO in lung tissue was significantly decreased in the 3‑MA and DEX groups compared with the model group (P<0.05). H&E staining demonstrated that 3‑MA and DEX each reversed the ALI. In addition, 3‑MA and DEX reduced the protein expression levels of LC3‑I, LC3‑II, ATG5, Rab7 and LAMP1. Also, RT‑qPCR results revealed that NF‑κB and TLR4 mRNA expression levels were clearly decreased in the 3‑MA and DEX groups compared with the model group. In conclusion, LPS‑induced ALI was effectively reversed by treatment with 3‑MA and DEX through the reduction of inflammation and autophagy and inhibition of the TLR4‑NF‑κB pathway.
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April-2018
Volume 15 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Ding D, Xu S, Zhang H, Zhao W, Zhang X, Jiang Y, Wang P, Dai Z and Zhang J: 3-Methyladenine and dexmedetomidine reverse lipopolysaccharide-induced acute lung injury through the inhibition of inflammation and autophagy. Exp Ther Med 15: 3516-3522, 2018
APA
Ding, D., Xu, S., Zhang, H., Zhao, W., Zhang, X., Jiang, Y. ... Zhang, J. (2018). 3-Methyladenine and dexmedetomidine reverse lipopolysaccharide-induced acute lung injury through the inhibition of inflammation and autophagy. Experimental and Therapeutic Medicine, 15, 3516-3522. https://doi.org/10.3892/etm.2018.5832
MLA
Ding, D., Xu, S., Zhang, H., Zhao, W., Zhang, X., Jiang, Y., Wang, P., Dai, Z., Zhang, J."3-Methyladenine and dexmedetomidine reverse lipopolysaccharide-induced acute lung injury through the inhibition of inflammation and autophagy". Experimental and Therapeutic Medicine 15.4 (2018): 3516-3522.
Chicago
Ding, D., Xu, S., Zhang, H., Zhao, W., Zhang, X., Jiang, Y., Wang, P., Dai, Z., Zhang, J."3-Methyladenine and dexmedetomidine reverse lipopolysaccharide-induced acute lung injury through the inhibition of inflammation and autophagy". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3516-3522. https://doi.org/10.3892/etm.2018.5832