Simulating sleep apnea by exposure to intermittent hypoxia induces inflammation in the lung and liver

Abstract

Sleep apnea is a breathing disorder that results from momentary and cyclic collapse of the upper airway, leading to intermittent hypoxia (IH). IH can lead to the formation of free radicals that increase oxidative stress, and this mechanism may explain the association between central sleep apnea and nonalcoholic steatohepatitis. We assessed the level of inflammation in the lung and liver tissue from animals subjected to intermittent hypoxia and simulated sleep apnea. A total of 12 C57BL/6 mice were divided into two groups and then exposed to IH (n = 6) or a simulated IH (SIH) (n = 6) for 35 days. We observed an increase in oxidative damage and other changes to endogenous antioxidant enzymes in mice exposed to IH. Specifically, the expression of multiple transcription factors, including hypoxia inducible factor (HIF-1α), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF-α), inducible NO synthase (iNOS), vascular endothelial growth factor (VEGF), and cleaved caspase 3 were shown to be increased in the IH group. Overall, we found that exposure to intermittent hypoxia for 35 days by simulating sleep apnea leads to oxidative stress, inflammation, and increased activity of caspase 3 in the liver and lung.

Figure 1

The effect of intermittent hypoxia on the expression of phosphorylated NF-κB in the liver ((a), P = 0.0247) and lung ((b), P = 0.0033). Results are reported as mean ± standard error, n = 6 per group. P value according to Student's t-test.

Figure 2

The effect of intermittent hypoxia on the expression of HIF-1α in the liver ((a), P = 0.0227) and lung ((b), P = 0.0086). Results are reported as mean ± standard error, n = 6 per group. P value according to Student's t-test.

Figure 3

The effect of intermittent hypoxia on the expression of TNF-α in the liver ((a), P = 0.0382) and lung ((b), P = 0.0171). Results are reported as mean ± standard error, n = 6 per group. P value according to Student's t-test.

Figure 4

The effect of intermittent hypoxia on the expression of iNOS in the liver ((a), P = 0.0091) and lung ((b), P = 0.0107). Results are reported as mean ± standard error, n = 6 per group. P value according to Student's t-test.

Figure 5

The effect of intermittent hypoxia on the expression of VEGF in the liver ((a), P = 0.0062) and lung ((b), P = 0.0184). Results are reported as mean ± standard error, n = 6 per group. P value according to Student's t-test.

Figure 6

The effect of intermittent hypoxia on the expression of cleaved caspase 3 in the liver ((a), P = 0.0022) and lung ((b), P = 0.0003). Results are reported as mean ± standard error, n = 6 per group. P value according to Student's t-test.