| Background and Objective:Intermittent hypoxia is the characteristic mode of hypoxia in Obstructive sleep apnea-hypopnea syndrome(OSAHS),which can easily cause oxidative stress,inflammation and cell apoptosis,and is closely related to the occurrence of cognitive impairment.The anti-oxidant and anti-inflammatory effects of sesamol have been widely studied in nervous system diseases and have neuroprotective functions.But there is no study of sesamol in cognitive impairment in rats with intermittent hypoxia,so a model of rats with intermittent hypoxia was established and sesamol intervention was used as a means in this study.Firstly the cognitive function of rats with intermittent hypoxia was tested.Secondly the neuroprotective mechanism of sesamol on cognitive impairment in rats with intermittent hypoxia is described from the aspects of oxidative stress,inflammation,apoptosis,cholinergic system damage,to provide new ideas and ideal nerve protective agent for the prevention and treatment of cognitive impairment.Content:1.A rat model of intermittent hypoxia was established and the effect of sesamol on cognitive function and neuronal apoptosis was explored.2.To observe the effect of sesamol on oxidative stress,inflammation and apoptosis-related proteins in hippocampal neurons of rat with intermittent hypoxia.3.To investigate the effects of sesamol intervention on the cholinergic system of hippocampal neurons in rat with intermittent hypoxia.Methods:Section 1:Adult male Wistar rats were selected as the research objects,and were randomly divided into unhandled control group(UC group),intermittent hypoxia group(IH group)and intermittent hypoxia + sesamol intervention group(IH+Sesamol group),each group was 2,4,6,and 8 weeks subgroups.The rats in the IH group and the IH+Sesamol group were given intermittent hypoxia respectively.The rats in the IH+Sesamol group were given intermittent hypoxia while being treated with sesamol.The UC group was given normal oxygen.The cognitive function of rats was observed by Morris water maze.The apoptosis of hippocampal neurons in rats was detected by Tunnel method.Section 2:The changes of SOD,MDA,TNF-α and IL-1β in hippocampal neurons of three groups were detected by ELISA.Immunohistochemistry and Western blot were used to detect the expression of Cyt C,AIF,Bax and Bcl-2 in the three groups of hippocampal neurons.Section 3:Immunohistochemistry and Western blot were used to detect the expression of Ch AT and ACh E in hippocampal neurons of the three groups of rats.Results:Section 1:1.Compared with UC group,the escape latency of rats in IH group and IH+Sesamol group was prolonged at 2,4,6 and 8 weeks of intermittent hypoxia,while the number of cross-platform crossing was decreased(P < 0.05);Compared with IH group,the escape latency of IH+ Sesamol group at 2,4,6 and 8 weeks was shortened,and the number of cross-platform crossing was increased(P < 0.05).The escape latency of IH+Sesamol group and IH group increased from 2 weeks to 8 weeks and reached the peak at 8 weeks with the prolongation of the duration of intermittent hypoxia(P<0.05),while the number of cross-platform crossing began to decrease at 2weeks and reached the lowest at 8 weeks with the prolongation of the duration of intermittent hypoxia(P<0.05).However,there were no differences in the escape latency and cross-platform crossing times in UC group at 2,4,6 and 8 weeks.2.Compared with UC group,the apoptosis index of hippocampal CA1 region of rats in IH group and IH+ Sesamol group was increased at 2,4,6 and 8 weeks after intermittent hypoxia(P < 0.05),but the apoptosis index of rats in IH+Sesamol group was significantly decreased at 2,4,6 and 8 weeks after intermittent hypoxia compared with IH group.The apoptotic index of IH+Sesamol group and IH group was prolonged from 2 weeks of intermittent hypoxia and reached the peak at 8 weeks(P< 0.05),but there was no difference in the apoptotic index of UC group at 2,4,6 and 8 weeks.Section 2:1.Compared with UC group,SOD level of rats in IH group and IH+Sesamol group decreased and MDA level increased at 2,4,6 and 8 weeks after intermittent hypoxia(P<0.05).However,compared with IH group,SOD level of rats in IH+Sesamol group increased at 2,4,6 and 8 weeks,while MDA level decreased at 2,4,6 and 8 weeks respectively.SOD level in IH+Sesamol group and IH group decreased from 2 weeks of IH and IH group,and reached the lowest level at 8 weeks(P<0.05).MDA level in IH+Sesamol group and IH group increased from 2 weeks of intermittent hypoxia,and reached the highest level at 8 weeks(P< 0.05).However,SOD and MDA levels in UC group had no difference at 2,4,6 and 8 weeks of IH group.2.Compared with UC group,TNF-α and IL-1β levels in IH group and IH+Sesamol group were increased at 2,4,6 and 8 weeks of intermittent hypoxia.Compared with IH group,TNF-α and IL-1β levels were decreased in IH+Sesamol group at 2,4,6 and 8 weeks(P<0.05).The levels of TNF-α and IL-1β in IH+ Sesamol group and IH group increased at 2 weeks(P<0.05),and reached the highest level at 8weeks(P<0.05),but the levels of TNF-α and IL-1β in UC group were not different at2,4,6 and 8 weeks.3.Compared with UC group,the levels of Cyt C,AIF and Bax in IH+ Sesamol group and IH group were increased and the levels of Bcl-2 were decreased after 2,4,6 and 8 weeks of intermittent hypoxia.Compared with IH group,the levels of Cyt C,AIF and Bax in IH+Sesamol group were decreased at 2,4,6 and 8 weeks,while the levels of Bcl-2 were increased(P<0.05).The levels of Cyt C,AIF and Bax in IH+Sesamol group and IH group increased at 2 weeks(P<0.05),and reached the peak at 8 weeks(P<0.05),while Bcl-2 decreased from 2 weeks and reached the lowest at 8weeks(P<0.05).However,there were no differences in Cyt C,AIF,Bax and Bcl-2 in UC group at 2,4,6 and 8 weeks.Section 3:1.Compared with UC group,after 2,4,6 and 8 weeks of intermittent hypoxia,the Ch AT level was decreased in IH group and IH+Sesamol group,while ACh E level was increased(P<0.05).Compared with IH group,Ch AT level increased and ACh E level decreased in IH+Sesamol group at 2,4,6 and 8 weeks of intermittent hypoxia(P<0.05).Ch AT level in IH+ Sesamol group and IH group decreased from 2 weeks and reached the lowest level at 8 weeks(P<0.05),while the level of ACh E increased from 2 weeks and reached the highest level at 8 weeks(P<0.05).However,there were no differences in Ch AT and ACh E levels in UC group at 2,4,6 and 8 weeks.Conclusion:1.Sesamol inhibits the apoptosis of hippocampal neurons and improves the cognitive function of rats with intermittent hypoxia.2.Sesamol inhibits oxidative stress of hippocampal neurons in rats with intermittent hypoxia,reduces inflammation and improves the function of cholinergic system.3.Sesamol mainly reduces the occurrence of mitochondrial apoptosis and regulates the function of cholinergic system by inhibiting oxidative stress and inflammation in hippocampal neurons of rats with intermittent hypoxia,and ultimately improves the cognitive function of rats with intermittent hypoxia. |
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