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Toll-Like Receptor 4 (TLR-4) Pathway Promotes Pulmonary Inflammation in Chronic Intermittent Hypoxia-Induced Obstructive Sleep Apnea

Jiao-Jiao Yang, Shu-Juan Wang, Xiaoling Gao, Bei Wang, Yan-Ting Dong, Yang Bai, Yan Chen, Jian-Nan Gong, Ya-Qiong Huang, Dong-Dong An

2nd Department of Clinical Medicine, Shanxi Medical University, Taiyuan, Shanxi, China (mainland)

Med Sci Monit 2018; 24:7152-7161

DOI: 10.12659/MSM.910632

Available online:

Published: 2018-10-07

BACKGROUND: Studies have shown that intermittent hypoxia mimics obstructive sleep apnea in causing pulmonary inflammation, but the mechanism is not yet clear.TLR-4 is a recognized proinflammatory factor, so the purpose of this study was to assess the function of TLR-4 in pulmonary inflammation induced by chronic intermittent hypoxia simulating obstructive sleep apnea.
MATERIAL AND METHODS: Healthy male Wistar rats were divided into 3 groups (8 in each group): the normoxia control group (CG), the intermittent hypoxia group (IH), and the TLR4 antagonist TAK242 treatment group (3 mg/kg, daily), with exposure durations of 12 weeks and 16 weeks (HI). The morphological changes of lung tissue were determined with hematoxylin-eosin (HE) staining. The expressions of the TLR-4 pathway in lung tissue were tested by Western blotting and RT-PCR. The levels of IL-6 and TNF-a in serum and lung tissue were detected by enzyme-linked immunosorbent assay (ELISA). The levels of SOD and MDA in lung tissue were detected by use of SOD and MDA kits, respectively.
RESULTS: After TAK242 treatment, damage to lung tissue was increased, and the expressions of TLR-4, MYD88, P65, IL-6, TNF-α, MDA, and SOD were decreased. Intermittent hypoxic exposure caused alveolar expansion, thickening of alveolar septum, and fusion of adjacent alveoli into larger cysts under intermittent hypoxia in a time-dependent manner. Compared with the CG and HI groups, the mean lining interval (MLI) become more thickened and the alveolar destruction index (DI) increased significantly in the IH group.
CONCLUSIONS: Chronic intermittent hypoxia causes pulmonary inflammatory response and the inflammatory pathway involved in TLR4 receptor may be one of the mechanisms that trigger lung inflammation.

Keywords: NF-kappa B, Pulmonary Disease, Chronic Obstructive, Sleep Apnea Syndromes, Toll-Like Receptor 4