1. Academic Validation
  2. TLR4 mediates inflammation and hepatic fibrosis induced by chronic intermittent hypoxia in rats

TLR4 mediates inflammation and hepatic fibrosis induced by chronic intermittent hypoxia in rats

  • Mol Med Rep. 2020 Aug;22(2):651-660. doi: 10.3892/mmr.2020.11134.
Zhi-Peng Lin 1 Hui-Li Lin 2 Xue-Ping Yu 1 Yi-Juan Zheng 1 Si-Yu Cheng 1
Affiliations

Affiliations

  • 1 Department of Infectious Diseases, The First Quanzhou Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
  • 2 Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China.
Abstract

Obstructive sleep apnea syndrome (OSAS) is a common and complex disorder that is associated with liver injury. Moreover, previous studies have revealed that chronic intermittent hypoxia (CIH) is associated with the development of non‑alcoholic fatty liver disease and hepatic fibrosis. However, the underlying molecular mechanisms remain largely unknown. The present study aimed to investigate whether chronic intermittent hypoxia induced hepatic fibrosis, in addition to determining its underlying mechanisms, in CIH model rats using immunohistochemistry, western blotting and reverse transcription‑quantitative PCR. The present results suggested that CIH caused hepatic fibrosis and increased the expression levels of interleukin (IL)‑1β, IL‑8, monocyte chemotactic‑1, tumor necrosis factor‑α, intercellular adhesion molecule‑1 and vascular cell adhesion molecule‑1 in the liver; these conditions could be reversed by Toll‑like receptor 4 (TLR4) short hairpin RNA lentivirus treatment. Moreover, immunohistochemistry and western blotting results indicated that TLR4 and NF‑κB expression levels were significantly increased in the CIH and CIH‑TLR4 empty vector lentivirus group. However, protein expression levels of TLR4, NF‑κB, inhibitor of NF‑κB and phosphorylated‑mitogen‑activated protein kinase (MAPK)‑1 in the hypoxia/reoxygenation group were significantly higher compared with the control group (P<0.05), and these results were reversed by the MAPK inhibitor U0126 in vitro. Collectively, the present preliminary results suggested that inflammation and the TLR4/NF‑κB/MAPK signaling pathway may be involved in CIH‑induced liver fibrosis.

Keywords

obstructive sleep apnea syndrome; chronic intermittent hypoxia; inflammation; liver fibrosis; Toll-like receptor 4.

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