| INTRODUCTION Insomnia is a common sleep disorder disease,is a variety of physical,mental and behavioral disorders of common clinical manifestations.Epidemiological investigation shows that 35.2% of the people in the western countries have different degrees of insomnia;The rate of insomnia in our country is as high as 10%~20%.Sleep disorders can cause serious harm to human health,long-term insomnia,not only lead to depression,but also lead to physical fatigue,cognitive dysfunction,even damage the immune system function,damage to the heart,interfere with blood sugar regulation,hormone secretion,and so on,even develop into depression.The cause of insomnia is related to genetic factors,living habits,environment,disease and mental and psychological factors.The study of its pathogenesis shows that the disorder of 5-HT,NE,GABA and other central nervous transmitter disorder in insomnia patients,edge system loop is abnormal.Sodium ferulate is a common drug of heart disease.foreign research and clinical observation have found that sodium ferulate has a sedative and hypnotic effect.however,it is not clear how sodium ferulate affects the central neurotransmitter 5-HT,NE,GABA and hippocampus neurons.OBJECTIVE Through establishing the model of insomnia rats,this study investigated the effect of sodium ferulate on sleep improvement and mechanism of sleep in rats with insomnia.MATERIALS AND METHODS 1.The effects of sodium ferulate on the general state and body weight of rats in rats were observed by intraperitoneal injection of p-chlorophenylalanine(PCPA).The effects of sodium ferulate on the sleep time of rats induced by pentobarbital sodium were observed.The levels of GABA,5-HT,NE,IL-1? and GABAARa1 m RNA expression were measured in rats,and the histopathological changes were observed.2.Effects of sodium ferulate on sleep function and serotonergic nervous system in rats.To investigate the effects of sodium ferulate on 5-HT levels in the prefrontal cortex,hypothalamus and hippocampus of rats.The effects of sodium ferulate on 5-HTP and 5-HT synthase(TPH)and metabolism of 5-HT in different brain regions of rats were measured by Elisa method.The effect of sodium ferulate on the sleep latency and sleep duration of rats was determined by Elisa method.The effect of sodium ferulate on 5-HTR1 A gene expression of 5-HT transporter gene Slc6a4 and 5-HT1 A gene in rat hypothalamus was investigated by RT-PCR.3.Effect of Sodium Ferulate on GABA Level in Model Rats.The brainstem,hypothalamus,frontal cortex and hippocampus were isolated from each group of rats by intraperitoneal injection of paclophenylalanine(PCPA).The rat brain stem and hypothalamus were measured by Elisa method.Leptospira and hippocampus,Glu level was determined by HPLC,GAD and GS were measured by Western Blot.4.Effects of sodium ferulate on rat hippocampal neurons and its mechanism.The effect of sodium ferulate on the mitochondrial injury of hippocampal neurons was investigated by MTT assay.The protective effect of sodium ferulate on hippocampal neurons was induced by mitochondria.The effect of sodium ferulate on the apoptosis of hippocampal neurons in rats was observed by TUNEL staining.The effects of sodium ferulate on mitochondria were observed by transmission electron microscopy(TEM).The effects of sodium ferulate on the apoptosis of hippocampal neurons in rats were observed by intraperitoneal injection of paclophenylalanine(PCPA)The effects of sodium ferulate on the activity of mitochondrial ATPase were determined.The m RNA and protein expression of Bcl-2 and Bax in hippocampus were detected by RT-PCR.The effects of sodium ferulate on the hippocampal neurons were investigated.mechanism.RESULTS 1.Sodium ferulate has a good effect on the general state,sleep quality and sleep-related neurotransmitters in PCPA insomnia rats.Sodium ferulate can effectively improve the general state of model rats,shorten sleep latency,prolong sleep time,increase GABA,5-HT,IL-1? and GABA m RNA relative expression,and can effectively reduce NE level;2.Effects of sodium ferulate on sleep function and serotonergic nervous system in rats.Sodium ferulate could significantly increase the concentration of 5-HT and TPH in the prefrontal cortex,hypothalamus and hippocampus of rats(P<0.05).In the combined application of ferulic acid group and 5-HTP group,the latency of sleep in the ferulic acid group and the 5-HTP group was shortened,and the duration of sleep duration was prolonged,but the difference was related to the blank control(P>0.05).When the combination of sodium ferulate and 5-HTP was applied,the sleep latency and sleep duration of the rats were significantly different from those of the blank group(P<0.05).The incubation period of PCPA group was significantly longer than that of ferulic acid group and blank control group(P<0.05),and the duration of sleep was significantly longer in patients with sodium ferulate(P<0.05).Compared with the blank group,the duration of sleep was significantly prolonged(P<0.05),and the duration of sleep in the PCPA group was significantly shorter than that in the blank group(P<0.05),and there was no significant difference between the combined group and the blank group(P>0.05).The concentration of 5-HIAA in the hippocampus,hypothalamus and prefrontal cortex of the ferulic acid group was significantly higher than that in the blank group(P<0.05).The ratio of hippocampus to hypothalamic 5-HIAA /5-HT Compared with the blank group,the difference was statistically significant(P<0.05).There was no significant difference in the ratio of 5-HIAA /5-HT between the prefrontal cortex and the blank group(P>0.05).The expression of Slc6a4 in the hypothalamus was significantly decreased and the expression of 5-HTR1 A was significantly increased in the ferulic acid group 3.Compared with the control group,the levels of GABA and GAD in the different brain regions of the model group were significantly decreased,the levels of Glu and GS were significantly increased,and the levels of GABA and GAD in the different brain regions of the rats were significantly increased Level,reduce the level of Glu in different brain regions,reduce hypothalamus,frontal cortex and hippocampus GS level,the brain stem GS regulation effect is not obvious;4.MTT assay was used to investigate the protective effect of sodium ferulate on mitochondrial injury in hippocampal neurons.The results showed that the survival rate of hippocampal neurons in mitochondrial injury rats was significantly lower than that in normal controls(P<0.05),and the hippocampal neurons The survival rate of the cells was higher than that of the model group(P<0.05).The results of TUNEL staining showed that sodium ferulate could decrease the apoptotic rate of hippocampal neurons in sleep deprived rats.RT-PCR results showed that sodium ferulate could promote Bcl-2 m RNA and protein expression,inhibit Bax m RNA and protein expression,Hippocampal neuronal apoptosis.CONCLUSIONS 1.The effect of sodium ferulate on the sleep quality of insomnia rats model after pcpa insomnia;This effect may be achieved by increasing the level of GABA,inhibiting the excitability of neurons,improving 5-ht,reducing ne level,and lowering ne level to inhibit the ne maintenance of NE.2.Sodium ferulate can enhance the excitability of 5-HTergic nervous system and inhibit the expression of 5-HT transporter by synerging 5-HTP,5-HTP,5-HT synthase inhibitor PCPA,Enhance the expression of 5-HT receptor and other mechanisms to play a role in improving sleep;3.The effect of sodium ferulate on GABA level in rats may be through the influence of GAD and GS expression in various parts of brain tissue,inhibit or promote the transformation between GABA and Glu,and change the Glu / GABA ratio balance.4.Sodium ferulate can inhibit the apoptosis of hippocampal neurons induced by sleep deprivation and improve sleep.The mechanism of action is related to the promotion of Bcl-2 m RNA and protein expression,inhibition of Bax m RNA and protein expression. |
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