Study On The Effect And Mechanism Of ShenDong YeAn Tablet In The Treatment Of Senile Chronic Insomnia Disorder Based On Orexin Signaling Pathway

Objective:1.To assess the clinical efficacy and safety of Shen Dong Ye ’An tablet(SDYA)in enhancing sleep quality among elderly patients diagnosed with chronic insomnia disorder.2.To investigate the impact of SDYA on orexin secretion and associated signaling pathways during the treatment of chronic insomnia disorder in older adults.Methods:1 To assess the clinical efficacy and safety of SDYA in enhancing sleep quality among elderly patients diagnosed with chronic insomnia disorderThe therapeutic efficacy was assessed by comparing the total score of the PSQI,individual scores of PSQI subscales,the overall score on the epworth sleepiness scale(ESS),comprehensive scores on traditional chinese medicine symptom scales,serum levels of OXA and OXB before and after a 28-day treatment period.Safety evaluation included liver and kidney function tests,as well as blood and urine routine examinations.2 To investigate the efficacy of SDYA in ameliorating sleep disturbances in aged rats model of sleep deprivationThe rat model of sleep deprivation was established by subcutaneously injecting d-galactose and PCPA,combined with water platform environmental deprivation.The effects of SDYA on the sleep latency,sleep duration,and circadian rhythm of the model rats were observed,with estazolam used as the positive control drug.3 To investigate the efficacy of SDYA on orexin secretion and related pathways in aged rats model of sleep deprivationThe distribution of OXA and OXB in the hypothalamus of rats in each group was assessed through immunohistochemical staining.Additionally,the contents of OXA and OXB were analyzed using elisa.Furthermore,the m RNA levels of proteins related to the orexin pathway were assessed using real-time quantitative PCR,while the expression of proteins associated with the orexin pathway was determined through western blot analysis.Results:1 The results of clinical efficacy and safety of SDYA in enhancing sleep quality among elderly patients with chronic insomnia disorderThe comparison between the experimental group and the control group before and after treatment revealed significant reductions(P<0.01)in the overall PSQI score,scores of individual PSQI indicators,total ESS drowsiness scale score,and total TCM symptom scale score.Furthermore,both groups exhibited significant decreases(P<0.01)in serum levels of OXA and OXB.No adverse reactions were observed throughout the study,and routine blood,urine,liver function tests as well as kidney function tests showed no apparent abnormalities within normal ranges pre-and post-treatment.2 The results of efficacy of SDYA in ameliorating sleep disturbances in aged rats model of sleep deprivationCompared with the control group,the model group experienced significant prolongation of sleep latency and reduction in sleep duration(P<0.01).Furthermore,compared with the model group,the SDYA group demonstrated shortened sleep latency and prolonged sleep duration(P<0.01).Compared with the control group,both in light and dark environments,autonomous activity time was significantly increased in the model group(P < 0.05).Furthermore,compared with the model group,the SDYA group had varying degrees of decreased autonomous activity time in both light and dark environments(P < 0.05).3 The results of efficacy of SDYA on orexin secretion and related pathways in aged rats model of sleep deprivationThe results of immunohistochemistry experiments showed that compared with the control group,the secretion of OXA and OXB in the model group was significantly increased.Furthermore,compared with the model group,the secretion of OXA and OXB in the SDYA group was significantly reduced.The results of elisa showed that compared with the control group,the OXA and OXB contents in the model group were significantly increased(P<0.01).Furthermore,compared with the model group,the OXA and OXB contents in the SDYA group were reduced(P<0.05).The results of real time PCR showed that compared with the control group,the m RNA levels of OXA,OXB,CREB,and PER1 in the model group were significantly increased(P<0.01).Furthermore,compared with the model group,the m RNA levels of OXA,OXB,CREB,and PER1 in the SDYA group were significantly reduced(P<0.01).The results of WB showed that compared with the control group,the OXA protein expression in the model group was significantly upregulated(P<0.01).Furthermore,compared with the model group,the OXA protein expression in the SDYA group was downregulated(P<0.05).Compared with the control group,the expression of OXB,CREB,and PER1 proteins in the model group was significantly upregulated(P<0.01)Furthermore,compared with the model group,the expression of OXB,CREB,and PER1 proteins in the SDYA group was significantly downregulated(P<0.01).Conclusion:1.SDYA can enhance the sleep quality of elderly individuals with chronic insomnia disorder,ameliorate daytime sleepiness and fatigue,and decrease serum levels of OXA and OXB without any noticeable adverse reactions,thus ensuring safety and reliability.2.SDYA can improve the sleep condition of sleep-deprived model rats by reducing sleep latency,prolonging sleep duration,and regulating circadian rhythm.3.SDYA can suppress the secretion of OXA and OXB in sleep-deprived model rats by down-regulating m RNA levels of OXA,OXB,CREB,and PER1;additionally decreasing protein expression of OXA,OXB,CREB,and PER1.