ABSTRACT
Objective:To evaluate the effects of sleep fragmentation on vascular cognitive impairment (VCI) and the relationship with central inflammation and oxidative stress in rats.Methods:Forty-eight male Sprague-Dawley rats, aged 8-10 weeks, weighing 210-240 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (group Sham), sham operation + sleep fragmentation group (group Sham+ SF), group VCI and VCI+ sleep fragmentation group (group VCI+ SF). VCI was induced by ligating bilateral common carotid arteries of anesthetized rats.In VCI+ SF and Sham+ SF groups, the sleep fragmentation model was established starting from day 26 after inducing VCI, and the contextual fear conditioning test and open field test were performed on day 29.After the end of the contextual fear conditioning test, the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-6) were determined by enzyme-linked immunosorbent assay, the hippocampal superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA) and iron contents were measured using microplate method, and the expression of nuclear factor-kappa B (NF-κB), caspase-3 and glutathione peroxidase 4 (GPX4) was determined using Western blot. Results:Compared with group Sham, the number of crossing lattices and standing on back legs and percentage of time spent freezing were significantly decreased, the contents of SOD and GSH-Px were decreased, the contents of MDA, IL-6, TNF-α and iron were increased, the expression of NF-κB and caspase-3 was up-regulated, and the expression of GPX4 was down-regulated in group VCI ( P<0.05). Compared with Sham+ SF and VCI groups, the number of crossing lattices and standing on back legs and percentage of time spent freezing were significantly decreased, the contents of SOD and GSH-Px were decreased, the contents of MDA, IL-6, TNF-α and iron were increased, the expression of NF-κB and caspase-3 was up-regulated, and the expression of GPX4 was down-regulated in group VCI+ SF ( P<0.05). Conclusion:Sleep fragmentation can aggravate VCI, and the mechanism may be related to the induction of central inflammation and oxidative stress, which leads to increased apoptosis and ferroptosis in hippocampal neurons of rats.