Effect Of Chronic Intermittent Hypoxia On The Expression Of HIF-1α And On NOS-2, VEGF And ET-1 In Mice

Objective: To explore the mechanism of the effect of chronic intermittent hypoxia, an important pathophysiological state of sleep apnea syndrome, on cardiovascular system. Methods: 30 ICR mice were divided in random into chronic intermittent hypoxia group, air mimic control group and blank control group. The chronic intermittent hypoxia group was exposed to intermittent hypoxia (hypoxia-reoxygenation, each circulation last 2minuts) for 30days. Immunohistochemistry was used to examine the expression of hypoxia inducible factor-1alpha (HIF-1α) and inducible nitric oxide synthase (NOS-2) in the myocardial cell. ELISA was used to measure the plasma concentration of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1). Results: The expression of HIF-1α in myocardial cell of the chronic intermittent hypoxia group significantly increased compared with that of the control groups(P<0.05). The expression of HIF-1α in myocardial cell of the air mimic control group was not significantly different from that of the blank control group. The plasma concentration of VEGF of the chronic intermittent hypoxia group (9.57±1.41)ng/ml was significantly higher than that of the blank control groups (8.10±0.62)ng/ml (P=0.006), and was significantly higher than that of the air mimic control group (8.32±0.99)ng/ml (P=0.016). While the plasma concentration of ET-1 of the chronic intermittent hypoxia group (3.31±0.81)ng/ml was significantly higher than that of blank control group (2.50±0.72)ng/ml (P=0.016), it was not significantly different from that of the air mimic control group (2.69±0.43)ng/ml (P>0.05). There was no significant difference between the expressions of NOS-2 in myocardial cell of all groups (P>0.05). Conclusion: Chronic intermittent hypoxia might enhance the expression of HIF-1α, and enhance the expression of VEGF and ET-1, which are target genes of HIF-1α, therefore affect on cardiovascular system.