Abstract: Objective To explore the mechanism of vessel endothelial dysfunction in rats under intermittent hypoxia (IH). Methods The respiratory simulation system was used to simulate IH. Sixty C57BL/6J rats (male) were randomized into control group and IH group. The rats of IH group were exposed to IH 8 hours per day for 6 weeks. The serum levels of hypoxia inducible factor (HIF)-1a and stromal cell derived factor (SDF)-1a were assessed by ELISA. The serum levels of reactive oxygen species (ROS) were detected in two groups. The serum expression of miR- 199a-5p was detected by realtime fluorescent quantitative PCR in two groups. The dual luciferase report system and point mutation test were used to verify target gene for HIF-1a. Results The serum levels of HIF-1a and SDF-1a were significantly higher in IH group than those of control group (μg/L: 1.60±0.02 vs. 1.19±0.02, 1 823.00±8.97 vs. 1 444.00±17.90, P＜0.01). The serum level of ROS was significantly higher in IH group than that of control group (U/mL: 487.66±35.73 vs. 211.57±23.82, P＜0.01). The serum level of miR-199a-5p expression was significantly lower in IH group compared to that of control group (1.31±0.07 vs. 3.47± 0.17, P＜0.01). The result of dual luciferase reporter gene detection confirmed that target gene of miR-199a-5p was HIF- 1a. Conclusion The serum level of miR- 199a- 5p is decreased first due to IH, and then its target gene (HIF- 1a) is increased. HIF-1a can induce the increased level of SDF-1a, and its receptor (CXCR-4 ) is also increased. Finally, HIF- 1a can increase the serum level of ROS, resulting in the endothelial dysfunction.

Key words: anoxia, hypoxia- inducible factor 1, alpha subunit, receptors, CXCR4, microRNAs, reactive oxygen species, intermittent hypoxia, stromal cell derived factor-1a, miR-199a-5p