| Objective: To make a chronic intermittent hypoxia animal model for study the impact of oxiracetam on cognitive impairment of obstructive sleep apnea-hypopnea syndrome (OSAHS) in rats. And to further approach the possible mechanisms of oxiracetam treatment of cognitive dysfunction of OSAHS in rats, for provide a theoretical basis for the drug-assisted treatment of cognitive dysfunction of patients with OSAHS .Methods: Twenty four adult male SD rats that were established chronic intermittent hypoxia model were randomly divided into control group (normal feeding for 4 weeks), chronic intermittent hypoxia group (CIH) (CIH for 4 weeks), reoxygenation group (normal feeding for 4 weeks after CIH for 4 weeks), drug group (consecutive oxiracetam treatment for 4 weeks after CIH for 4 weeks). First, all rats were taken Morris water maze test, and were observed behavior alteration. Second, determined the expression of acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) of the rat hippocampal CA3 area by use of immunohistochemistry and image analysis, while observed ultrastructural changes of rat hippocampus of the four groups of rats by electron microscopy, and evaluated the spatial learning and memory function of the four groups of rats.Results:1. Morris water maze performance (positioning navigation test): From the first day, the escape latency of rats in the chronic intermittent hypoxia group was longer than the control group, the reoxygenation group and the drug group (p <0.05), the escape latency of rats in the reoxygenation group was longer than the control group (p <0.05), that in the drug group was significantly shorter than the reoxygenation group (p <0.05), the escape latency of the drug group of the first day close to the control group, no significant difference (p> 0.05), the escape latency of the drug group of the second day to the fifth day was longer than the control group (p <0.05).2. Morris water maze memory performance: the number of times of acrossing the platform in the chronic intermittent hypoxia group was significantly reduced than that in the control group (p <0.05), and that in the reoxygenation groups was significantly increased than that in the chronic intermittent hypoxia group (p <0.05 ), but lower than the control group (p <0.05), and that in the drug group was increased than that in the reoxygenation group, close to the control group, there was no significant difference (p> 0.05). The percentage of time spenting on acrossing the target quadrant in the total of swimming time in each group compared: the chronic intermittent hypoxia group was significantly reduced than in the control group (p <0.01), the reoxygenation group was significantly increased than the chronic intermittent hypoxia (p < 0.05), but it was still significantly reduced than the control group (p <0.05), the drug group was significantly increased than in the reoxygenation group (p <0.05), close to the control group, there was no significant difference (p> 0.05).3. The expression of AchE of rat hippocampal CA3 area of four groups compared: the average optical density (IOD / area, that is, IOD sum / area sum) of positive expression of AchE of the chronic intermittent hypoxia group was significantly fewer than the control group (F = 11.23, p <0.05), the reoxygenation group was higher than the chronic intermittent hypoxia group (p <0.05), and fewer than the control group (p <0.05), the drug group was higher than the reoxygenation group (p <0.05 ), close to the control group, there was no significant difference (p> 0.05).4. The expression of ChAT of rat hippocampal CA3 area of four groups compared: the average optical density (IOD / area, that is, IOD sum / area sum) of positive expression of ChAT of the chronic intermittent hypoxia group was significantly fewer than the control group (F = 9.63, p <0.05), the reoxygenation group was higher than the chronic intermittent hypoxia group (p <0.05), and fewer than the control group (p <0.05), the drug group was higher than the reoxygenation group (p <0.05 ), close to the control group, there was no significant difference (p> 0.05). 5. Electron microscopy observation shows that the neurons of hippocampal CA3 of rat in the chronic intermittent hypoxia group have many ultrastructural changes such as loose array, increased electron density of cytoplasm, mitochondrial swelling, these changes in the reoxygenation group are improved, failed to fully recover; the neurons of hippocampal CA3 of rat in the drug group close to normal.Conclusion:1. Chronic intermittent hypoxia in rats can cause a decline in learning and memory function, learning and memory function of rats are improved after remove hypoxia-factor, but still lower than normal.2. Oxiracetam can significantly improve cognitive impairment of chronic intermittent hypoxia in rats , the possible mechanisms is that Oxiracetam affect on the hippocampus selectivly, excite acetylcholine nerve pathway and repair the hippocampal CA3 area neurons, thus improve learning and memory function. |
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