Changes Of ?7nAChR Expression In Hippocampus Of OSAS Rats

Objective: The rat model of OSAS(Obstructive sleep apnea syndrome,OSAS)was simulated by CIH(chronic intermittent hypoxia,CIH).The behavioral changes of OSAS rats,the pathophysiological changes of hippocampus,and the localization and expression of ?7nAChR(?7 nicotinic acetylcholine receptor,?7nAChR)in hippocampal neurons were observed after administration of ?7nAChR agonists.Make clear the change of ?7nAChR expression in hippocampus of OSAS rats.Methods: Forty-eight healthy male Sprague-Dawley rats were randomly divided into four groups.There were 12 rats in normal control group,12 rats in OSAS model group,12 rats in ?7nAChR agonist group and 12 rats in saline control group.Chronic intermittent hypoxia was used to simulate the establishment of OSAS rat model.Rats in normal control group were not treated with any treatment.Rats in ?7nAChR agonist group were injected intraperitoneally with PNU-282987(3mg/kg)before modeling every day.The saline control group was treated with 0.9% normal saline(1ml/kg)for 4 weeks at the same time.The spatial learning and memory ability of rats in each group was measured by Morris water maze(MWM)water maze,and the pathological changes of hippocampal neurons in each group were observed by hematoxylin-eosin stainin(HE).The distribution of?7nAChR positive cells in rat hippocampus was detected by immunohistochemistry(IHC)and the expression of ?7nAChR protein in hippocampus in rats hippocampus was detected by protein imprinting(Western blotting,WB).Results: The main results were as follows:(1)the symptoms of head up breathing,suffocating awakening,abdominal respiration deepening,activity decreasing and respiration increasing were observed in OSAS group,and the experimental rats were exposed to hypoxia.The blood pressure saturation of caudal artery was(70.39±1.84)%,while the oxygen saturation of caudal artery was(95.64±1.20)% when deoxygenated in air environment,and the decrease of blood oxygen saturation was obvious and>4%.In accordance with OSAS model construction standard;(2)The results of MWM experiment:compared with the normal group and the rats treated with ?7nAChR agonists,the escape latency of the OSAS group was prolonged and the number of times of crossing the hiddenplatform was decreased,which indicated that the rats had cognitive impairment in learning and memory;(3)the results of HE: CIH could cause hippocampal tissue injury,and the number,arrangement and dispersion of neurons in hippocampal CA1(hippocampal CA1 subfield,CA1)and CA3(hippocampal CA3 subfield,CA3)regions of OSAS group were decreased,the cell density was decreased,and the nucleus was decreased,and the karyopyknosis.Psychosis,sparse cytoplasm and unclear boundary;(4)the results of IHC:?7nAChR was mainly distributed on the cell membrane of hippocampal CA1 region and CA3 region,and also expressed in cytoplasm,and the positive expression was brownish yellow granular substance.the expression of ?7nAChR in hippocampal CA1 region and CA3 region in OSAS group was lower than that in normal group and intervention group.The difference was statistically significant(P<0.05);(5)the results of WB: the expression of ?7nAChR protein in hippocampus of OSAS group was significantly lower than that of normal group and intervention group(P<0.05);(6)The escape latency was negatively correlated with the expression of ?7nAChR in hippocampus,and the number of crossing platform was positively correlated with the expression of ?7nAChR in hippocampus.Conclusion: The expression of ?7nAChR in hippocampus of OSAS rats was decreased,which was correlated with the function of learning and memory.?7nAChR agonists could increase the expression of ?7nAChR in hippocampus of OSAS rats and improve their cognitive impairment.