The damage mechanism of intermittent hypoxia in disrupting the circadian rhythm and metabolism of idiopathic pulmonary interstitial fibrosis.

Clinically, IPF overlapping OSA has a high incidence, few studies have conducted in-depth research on the overlapping mechanism of them.73 male 4-6-week-old C57 mouse were divided into the normobic feeding group, and the intermittent hypoxia(IH) group. After 14 days, some mouse underwent bleomycin(BLM) injection for the pulmonary fibrosis model. On the second day, and the IH group resumed intermittent hypoxic exposure (including IH as well as BLM + IH groups). After 21 days, the remaining mouse (CTRL, BLM, IH, BLM+ IH) were randomly divided into two groups of each module and sacrificed at 8:00 a.m. and 8:00 p.m.IH could aggravate the pathological damage and collagen synthesis of pulmonary fibrosis caused by BLM in mouse. Under the IH model, a variety of metabolites losed their circadian rhythms, mainly of which were lipids. Overlapping the pulmonary fibrosis model after IH showed significant changes in metabolic pathways. At night, BLM vs BLM+IH had significant differences in lipids, especially fatty acyl, glycerol phospholipids, and sterol esters were most obviously downregulated at night. In the bleomycin model after overlapping intermittent hypoxia, fatty acid synthesis is inhibited. There was a positive correlation between 3-hydroxydecanoylcarnitine, L-caprylylcarnitine, oleoylcarnitine, and tetradecanoylcarnitine, suggesting that the decline of these four substances may be a potentially specific biomarker for pulmonary interstitial fibrosis combined with sleep apnea. It was also suggested that after overlapping intermittent hypoxia, the mouse with pulmonary fibrosis showed abnormal metabolism and energy supply disruption.