Abstract
Objective To investigate the effect of intermittent hypoxia on neuronal apoptosis and inducible nitric oxide synthase (iNOS) expression in rat hippocampus, in order to explore the potential mechanism of hippocampal neuronal apoptosis induced by intermittent hypoxia. Methods Twenty-four Wistar male rats (280-350 g) were randomly divided into three groups: the normal control, intermittent normoxia and intermittent hypoxia group (n=8 each). The animal model of intermittent hypoxia was established by an automated nitrogen/oxygen profile system. The three groups were respectively exposed to continuous normoxia (21%O2), cyclical normoxia (21%O2), and cyclical hypoxia [alternating between normoxia (21%O2) and hypoxia (5%O2), every 120 seconds] throughout the eight hours of light time(8∶00-16∶00). The rats were dissected and the hippocampus was removed at the end of the designated duration of exposures for six weeks. TdT-mediated dUTP nick end labeling (TUNEL) was used to detect the apoptotic rate of the hippocampus region in each group. Reverse transcription-PCR, immunohistochemistry (IHC) and Western blotting were used to examine mRNA and protein expressions of iNOS in the hippocampus tissue. Results The apoptotic rate of hippocampal neurons was higher in intermittent hypoxia group than in intermittent normoxia group 〔(28.236±0.081)% vs. (9.341±0.026)%, P<0.05〕. The mRNA and protein expressions of iNOS were higher in intermittent hypoxia group than in intermittent normoxia group (3.394±1.344 vs. 0.125±0.040, 7.793±0.052 vs. 1.356±0.039, both P<0.05). Conclusions Intermittent hypoxia can induce hippocampal neuronal apoptosis in rats, accompanied by the upregulation of iNOS gene transcription and protein expression, which indicates that iNOS may involve in the process of hippocampal neuronal apoptosis induced by intermittent hypoxia. Key words: Sleep apnea, Obstructive; Apoptosis; Nitric oxide synthase
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