Chaihu Jia Longgu Muli Decoction On Improving Sleep Mechanics Of Sleep Deprived Mice During Perimenopause

ObjectivePerimenopause is the period from the age of about 45 to 12 months after menopause.Insomnia is one of the most common neuropsychiatric symptoms associated with perimenopausal period,and is also one of the core symptoms for perimenopausal women to seek treatment.In view of the adverse reaction of sedative hypnotic drugs,most women did not take effective intervention measures to treat perimenopausal insomnia.Traditional Chinese medicine has obvious advantages in the treatment of perimenopausal insomnia through syndrome differentiation.Traditional Chinese medicine from the liver treatment of perimenopausal syndrome,the use of soothing the liver,relieving depression and calming the nerves prescription to treat perimenopausal insomnia.CJLM70E is a representative prescription for relieving the depression of the liver.It comes from Zhang Zhongjing’s Treatise on Febrile Diseases in the Eastern Han Dynasty.It has the functions of relieving the depression of the liver,relieving Shaoyang,and calming the mind in the important town.The previous research results of our laboratory showed that CJLM70E can prolong the sleep time of ovoectomized animals,and its material basis is 70%effective part of alcohol extraction（CJLM70E）.But the mechanism is not entirely clear.Therefore,this study studied the improvement of sleep duration and wake-sleep rhythm in perimenopausal mice by CJLM70E,as well as the relevant mechanism.MethodsOn day 49 after VCD injection,the 24-hour sleep time of mice in the administration group was significantly higher than that in the model group（p<0.001）;Compared with VCD group,the 24 h activity times of CJLM70E group and E2 group were significantly decreased（p<0.001）.Compared with Control group,24h sleep time of VCD group was significantly decreased（p<0.05）;Compared with VCD group,24 h sleep time of CJLM70E group and E2 group was significantly increased（p<0.001）.Compared with the perimenopausal model,perimenopausal sleep-deprived mice had impaired ovarian morphology and significantly increased the number of atretic follicles（p<0.05）,the ovarian coefficient was significantly decreased（p<0.05）,the serum GABA and E₂ level was significantly decreased（p<0.05）,the density of Erα,Per2,PI3K,Akt and GABA in hypothalamus decreased significantly（p<0.05）.Compared with perimenopausal sleep-deprived mice,perimenopausal sleep-deprived CJLM70E mice showed better oocyte morphology and significantly lower number of atretic follicles（p<0.001）,the ovarian coefficient was significantly increased（p<0.05）,serum GABA and E₂level was significantly increased（p<0.01）,the density of Erα,PI3K,Akt and GABA in hypothalamus was significantly increased（p<0.05）.Compared with mice with perimenopausal sleep deprivation,LY294002 mice with perimenopausal sleep deprivation had oocyte pyknosis,zona pellucida dilation,and an increased number of atretic follicles（p<0.05）,the uterine coefficient and ovarian coefficient decreased（p<0.05）,the serum GABA and E₂ level was significantly decreased（p<0.05）,the density of Erα,PI3K,Akt,and GABA in hypothalamus decreased significantly（p<0.05）.Compared with perimenopausal mice given CJLM70E with sleep deprivation,perimenopausal mice given CJLM70E and LY294002 had significantly lower uterine and ovarian coefficients（p<0.001）,the serum GABA and E₂level was significantly decreased（p<0.05）,the density of Erα,PI3K,Akt,and GABA in hypothalamus decreased significantly（p<0.05）.ConclusionCJLM70E can significantly increase the sleep time of perimenopausal mice and improve the fragmented sleep of perimenopausal mice.CJLM70E improves sleep in perimenopausal mice by regulating the ERα/PI3K/Akt/GABA signaling pathway.