| Background and Objectives:Infantile spasms(IS)is one of the most common catastrophic epilepsy syndromes in childhood.The syndrome is characterized by spasms,hypsarrhythmic EEG,and mental retardation.Its onset has a circadian rhythm.Melatonin,an amine hormone secreted by the human body,is regulated by the circadian rhythm and also regulates the circadian rhythm.The key point in the formation of circadian rhythm is the expression of circadian rhythm genes,among which the core genes are BMAL1 and CLOCK genes,as well as their target genes Per and Cry genes.At present,the pathogenesis of infantile spasms is not completely clear,but the related literature reports that epilepsy is closely related to melatonin and circadian rhythm.Therefore,this experiment aims to explore the relationship between infantile spasms and melatonin and circadian rhythm,and further explore new treatment options.Methods:? Children with infantile spasms were selected from the General Hospital of the People's Liberation Army from March 2017 to September 2017.According to the diagnostic criteria for infantile spasms in 2010,39 patients were identified as the case group.Among the common patients,42 patients without epilepsy and neurological psychiatric diseases were selected as the control group.The serum melatonin(MT),serotonin(5-hydroxytryptamine,5-HT),prolactin(PRL)and nitric oxide(NO)levels were detected by enzyme-linked immunosorbent assay(ELISA).And the levels of MT,5-HT,PRL and NO wrer compared between the case group and the control group.Differences before and after ACTH treatment in the case group were also compared.2.9 male Sprague-Dawley rats and 18 female Sprague-Dawley rats were selected.Some female rats were given prenatal stress after pregnancy,and NMD A injection was given to their offspring to establish a rat model of infantile spasms.The frequency and severity of seisures were recorded,and the expression of the circadian rhythm genes CLOCK,BMAL1,Perl,Per2,Cry1,Cry2 of the hypothalamus ware analyzed by Western blot.Results:1:The serum levels of MT(7.1±1.9)pg/ml and 5-HT(1183.3±258.9)mIU/L in the case group were significantly lower than those in the control group(P<0.05),while the levels of PRL(523.1±109.4).mIU/L and NO(101.3±22.1)?mol/L were significantly higher than the control group(P<0.05).The levels of MT(9.2±1.9)pg/ml and 5-HT(1366.0±236.9)mlU/L in the case group were higher than those before treatment(P<0.05),and the level of PRL(408.2±93.4)mlU/L is lower than that before treatment.(P<0.05).The level of NO(96.3±21.9)?mol/L was not significantly different from that before treatment(P=0.261).? Compared with the healthy control group,the seizure latency and clinical score of the seizures in the prenatal stress+NMDA group were significantly different.Comparison of prenatal stress+NMDA group,the seizure latency and clinical scores of prenatal stress+NMDA+ACTH group,prenatal stress+NMDA+melatonin group and prenatal stress+NMDA+ACTH+melatonin group were significantly different.Compared with the healthy control group,the circadian gene CLOCK?BMAL1?PER1?PER2?CRY1?CRY2 in all prenatal stress+NMDA groups showed low expression status,and ware expressed increasingly after ACTH or(and)MT treatment.Conclusion:The levels of serum MT,5-HT,PRL and NO in children with infantile spasms can be significantly abnormal.After ACTH treatment,MT and 5-HT levels are obviously increased,PRL levels are falling,and NO levels are unchanged.It is speculated that the abnormalities and interactions of melatonin and related hormone may play an important role in the pathogenesis of infantile spasms.The circadian rhythm factor in the rat model of infantile spasms can be in low expression state.While the expression levels can be seen a significant increase after the treatment of ACTH or(and)MT.So the low expression level of circadian rhythm factors may be the pathogenesis basis of infantile spasms. |
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