| Objectives By establishing a rat model of intermittent hypoxia,the pathophysiological characteristics of intermittent hypoxia in sleep apnea hypopnea syndrome were simulated,and the effect of intermittent hypoxia on cognitive function of rats were investigated;The effects of PI3K/AKT signaling pathway and melatonin antioxidant on the expression level and cognitive function of PI3K/AKT signaling pathway-related proteins and cognitive function in hippocampal neurons of intermittent hypoxia rats were investigated by injecting PI3K/AKT inhibitor and melatonin antioxidant.Methods The choice of 68 adult male Wistar rats(weight170±10)were randomly divided into four groups: normal group(UC group),intermittent hypoxia group(IH group),inhibitor group(PI3K group),and melatonin group(MT group).Each group was divided into 4 time subgroups(2W,4W,6W and 8W).The inhibitor group and the melatonin group were injected with PI3K/AKT inhibitor GDC-0084(0.2mg/kg)and melatonin ML221(10mg/kg)intraperitoneal injection at 7:30 am each day.After the injection for 30 min,the rats were put together in the intermittent hypoxic box with a daily exposure time of 7 hours;rats in the UC group were placed in a hypoxic box and continuously given 21% oxygen-concentrated air.At the time of 2W,4W,6W,8W,Morris water maze test was used to detect the learning and memory function of rats.Four rats were randomly sacrificed in each group.ELISA was used to detect the levels of oxidative stress indicators in the hippocampus and serum of the sacrificed rats in each group.Immunohistochemical real-time fluorescence quantitative PCR was used to detect the expression of PI3K/AKT signaling pathway-related proteins and nucleic acids in the hippocampal CA1 area of each group.Results 1 Morris water maze results: there was a statistically significant difference between the four groups in the escape latency period and the percentage of time crossing the target quadrant(Pbetween group<0.05);In terms of escape latency period: inhibitor group>intermittent hypoxia Group>melatonin group>Normal group,in terms of the percentage of time across the target quadrant: Inhibitor group<Intermittent hypoxia group<melatonin group<Normal group,and within 8 weeks of intermittent hypoxia,with the extension of intermittent hypoxia time,intermittent hypoxia group,inhibitor group In the melatonin group,the escape latency period was prolonged,and the percentage of time to cross the target quadrant was shortened(Ptime<0.05),and there was an interaction between the groups and time(Pinteraction<0.05).2 Oxidative stress test results: there were statistically significant differences in ROS,MDA and SOD levels in hippocampal tissues between the four groups(Pbetween group>0.05),ROS and MDA levels in the inhibitor group>Intermittent hypoxia group>Melatonin group>normal group,SOD level in inhibitor group>Intermittent hypoxia group>Melatonin group>normal group,and within 8 weeks of intermittent hypoxia,with the extension of intermittent hypoxia time,In the intermittent hypoxia group,the inhibitor group and the melatonin group,the levels of ROS and MDA in hippocampal tissues increased,while SOD levels decreased(Ptime<0.05),there was interaction between groups and time(Pinteraction<0.05).3 Results of nucleic acid and protein related to PI3K/AKT signaling pathway neurons in the hippocampus of rats: that there were statistically significant differences in the expression of PI3 K and AKT nucleic acids and proteins in the neurons of hippocampus among the four groups(Pbetween group<0.05),and the melatonin group>intermittent hypoxia group>inhibitor group>normal group,and within 8 weeks of intermittent hypoxia,with the extension of intermittent hypoxia time,the expression of p-pi3 k,p-akt nucleic acid and protein in the hippocampal of the rats in the intermittent hypoxia group and the melatonin group decreased(Ptime<0.05),there was interaction between groups and time(Pinteraction<0.05).4 Results of Nrf2,HO-1 nucleic acid and protein in nerve cells of rat hippocampal:there were statistically significant differences in expression of Nrf2,HO-1 nucleic acid and protein in nerve cells of rat hippocampus among the four groups(Pbetween group<0.05),the melatonin group>intermittent hypoxia group>inhibitor group>normal group,and within 8 weeks of intermittent hypoxia,with the extension of intermittent hypoxia time,the expression of Nrf2,HO-1 nucleic acid and protein in neurons of hippocampal nerve cells decreased in the inhibitor group,intermittent hypoxic group and melatonin group decreased(Ptime<0.05),and there was an interaction between the groups and time(Pinteraction<0.05).Conclusions 1 Intermittent hypoxia causes oxidative stress in the hippocampus of rats,activates the PI3K/AKT signaling pathway,exerts anti-oxidative stress,and improves the cognitive function of rats.2 Melatonin can play the role of anti-oxidative stress and improve cognitive function by regulating the expression levels of related factors in PI3K/AKT signaling pathway.Figure17;Table14;Reference 129... |
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