Objective: To examine the pathological change and intima thickness of thoracic aorta, detect the serum concentration of hypoxia-inducible factor-1α (HIF-1α), oxidized LDL (ox-LDL), and pentraxin 3 (PTX3) in the rat model of chronic intermittent hypoxia (CIH), and to determine the effect of CIH on endarterium injury and its possible pathway.
Methods: Twenty-four male Sprague-Dawley (SD) rats were divided into 4 groups: a CIH+Nacetylcysteine (NAC) group, a CIH+normal saline (NS) group, a CIH control group and a control group. CIH rats were subjected to alternating cycles of hypoxia (6%-8% O2 in N2 for 20-25 s) and normoxia (21% O2 in N2 for 2 min) every 180 s for 7 h/d. Rats in the control group were not treated. Rats in the CIH+NAC group were treated with NAC [800 mL/(kg.d)] intraperitoneal injection, and rats in the CIH+NS group were treated with NS [5 mL/(kg.d)] intraperitoneal injection. After 42 day treatment, the rats were sacrificed, blood taken, and thoracic aorta cut off. The serum concentration of HIF-1α, ox-LDL, and PTX3 were detected by ELISA. The thickness of intima was taken by computer digital image analysis.
Results: Vascular endothelial cell injury and detachment were found in the thoracic aorta in the CIH and the CIH+NS group. The intima in the CIH and the CIH+NS group was thicker than that in the control and the CIH+NAC group (P<0.001). The serum concentration of HIF-1α, ox-LDL, and PTX3 in the CIH and the CIH+NS group was higher than that in the control and the CIH+NAC group (P<0.001). The serum concentration of HIF-1α, ox-LDL, and PTX3 was pairwise positive correlation, and the serum concentration of ox-LDL and PTX3 was positively correlated with the thickness of intina (P<0.001).
Conclusion: The vascular endothelial cell injury and endarterium thickening can be induced by CIH. It is an important pathway that CIH activates oxidative stress and elevates the levels of HIF- 1α, ox-LDL, and PTX3.