Correlation of the expressions of serum hypoxia-inducible factor-1α and brain-derived neurotrophic factor with cognitive impairment in Wistar rats under different hypoxia conditions / 医学研究生学报

ABSTRACT

Objective Obstructive sleep apnea hypopnea syndrome (OSAHS) often causes damage to multiple systems, especially to the central nervous system, inducing cognitive dysfunction.This study aims to explore the possible correlation of the expressions of serum hypoxia-inducible factor-1α (HIF-1α) and brain-derived neurotrophic factor (BDNF) with cognitive impairment in rats under different hypoxia conditions.Methods Twenty-four Wistar rats were equally randomized into a normal control, a chronic intermittent hypoxia (CIH), and a chronic continuous hypoxia (CCH) group.The rats of the CIH group were placed in a hypoxia chamber filled with N2 and air, the oxygen concentration switched from (7±0.5)% to 21%, 1.5 minutes for each state and 4 minutes for each cycle, while those of the CCH group were placed in another hypoxia chamber with the oxygen concentration of (7±0.5)%, 8 hours a day and all for 30 days.Then we recorded the body weight of the rats, detected the expressions of serum HIF-1α and BDNF by ELISA, and observed the changes of behavior by Morris water maze test and those of the hippocampal morphological structure by HE staining.Results At 30 days after modeling, the body weight of the rats was significantly decreased in the CIH and CSH groups as compared with the normal control ([195.75±6.497] and [180.88±12.017] vs [218.63±15.287] g, P<0.05).Positioning navigation showed that the escape latency was significantly longer in the hypoxia models than in the controls (P<0.05), even longer in the CIH than in the CCH group (P<0.05).Spatial exploration test manifested a lower frequency of crossing the platform in the CIH and CCH groups than in the control ([2.63±1.45] and [3.22±1.30] vs [4.97±0.47] times, P<0.05).The expression levels of serum HIF-1α and BDNF were significantly higher in the CIH ([36.14±9.34] and [1625.34±332.44] pg/mL) and CCH ([27.27±6.88] and [1204.07±363.81] pg/mL) than in the normal control group ([14.11±4.06] and [1036.40±124.48] pg/mL) (P<0.05), even higher in the CIH than in the CCH group (P<0.05).HE staining exhibited scattered and disorderly arrangement of hippocampal neurons in the model rats, with unclear nuclear membrane, pyknosis of the nuclei, darkly stained cytoplasm, and some damaged cells.More obvious absence and vacuolization of some cells were observed in the rats of the CIH group.Conclusion Chronic hypoxia inhibits the growth and development of rats and induces cognitive dysfunction.High-level HIF-1α in chronic intermittent hypoxia indicates hypoxia-stress of the body, while compensatory increase of serum BDNF may be involved in neuronal cell damage regulation.