| Objective:Perimenopausal syndrome is a common and frequently-occurring disease in women,which seriously affects women's physical and mental health.Hormone replacement therapy is widely used in domestic and overseas,but there are many contraindications and adverse reactions.Chaihu Siwu Decoction is an empirical prescription for the treatment of perimenopausal syndrome by Professor Mei Guoqiang,a master of Traditional Chinese medicine.Therefore,the purpose of this research is to explore the mechanism of Chaihu Siwu Decoction in the treatment of perimenopausal syndrome through kisspeptin/GPR54/Gn RH pathway.This research can lay a good foundation for further research,and also provide a corresponding basis for the development of new drugs in the future.Methods:1.Theoretical research:By combing the records of diseases and syndromes related to perimenopausal syndrome in ancient books,this paper summarizes professor Mei Guoqiang's main views on the pathogenesis of perimenopausal syndrome,and discusses the origin of the prescriptions of Chaihu Siwu Decoction,so as to clarify the theoretical basis of TCM in the treatment of perimenopausal syndrome.2.Experimental research:(1)Methods of making and evaluating models of perimenopausal syndrome:Using ovariectomized rats(OVX)as the model of perimenopausal syndrome.Judge whether the model is successfully established by observing the cell morphology in the vagina.(2)Methods of animal grouping and drug intervention:72 female rats with good mental state,similar body weight and normal estrous cycle were selected for the experiment.After the adaptive feeding,they were randomly divided into6 groups:sham operation group,model group,estradiol valerate group,Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups,with 12 rats in each group.In the sham operation group,only a small amount of adipose tissue near both ovaries was removed,and the ovaries were kept.The other groups were ovariectomized.After excluding the rats that died from anesthesia,wound infection,and estrus after surgery,we selected 60 rats that met the requirements for inclusion in the experiment,and divided these rats into 6 groups,with 10rats in each group.Starting from the 14th day after surgery,relevant drugs were administered for 28 days.The drug dosage was converted according to the equivalent clinical dose of adults.The sham operation group and model group were given stroke-physiological saline solution.The Estradiol Valerate group was given the suspension of estradiol valerate tablets at the dose of 0.08mg/kg·d.The high,medium and low dose groups of Chaihu Siwu Decoction were respectively given 22.12g/kg·d,11.06g/kg·d and 5.53g/kg·d.(3)Detection of related indicators:the appearance signs,body weight,food intake,water intake and activities of rats in each group were observed;The changes of uterine weight and uterine index were observed in each group.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of uterus in each group.The levels of E2,FSH,LH in serum and FSH,LH in pituitary homogenate were determined by enzyme linked immunosorbent assay(ELISA).Reverse Transcription-Polymerase Chain Reaction(RT-PCR)was used to detect the m RNA expression changes of ER?m RNA in uterus,Gn RH-R m RNA in pituitary,ER?m RNA,KISS-1 m RNA,GPR54 m RNA and Gn RH m RNA in ARC region of hypothalamus.Western Blot was used to detect the changes of ER?in uterus,Gn RH-R in pituitary,ER?,kisspeptin,GPR54 and Gn RH in ARC region of hypothalamus.Results:1.Theoretical research:The records of perimenopausal syndrome in ancient books are mainly found in"hysterian","lily disease","menorrhagia in middle-aged and elderly","postmenopausal menstruation","depression syndrome","insomnia","palpitation","fatigue"and so on.Clearly recorded perimenopausal women of the disease is the most"irregular vaginal bleeding",other diseases are scattered in the medical literature.Professor Mei Guoqiang believes that the pathogenesis of perimenopausal syndrome mainly includes the following three aspects:(1)Chong and Ren Channel deficiency,Yin and Yang imbalance;(2)Shaoyang Gallbladder Channel of Foot stasis and fire rushing;(3)Shaoyang Sanjiao Channel of Hand is unfavorable,phlegm dampness or damp heat inside.Chaihu Siwu Decoction has the functions of operating the cardinal,clearing the fire,cooling blood and calming the liver,etc.It takes into account the two systems of Shaoyang Channel,Chong and Ren Channel,and relieve various symptoms of perimenopausal syndrome.2.Experimental research:Experiment 1:Influence of Chaihu Siwu Decoction on general condition of perimenopausal syndrome model rats(1)Changes in appearance and physical signs:The rats in sham operation group had well-proportioned body,dense and shiny hair,good mental state and sensitive reaction.The rats in the model group had thicker fat tissue in the abdomen and buttocks,scattered hair,decreased gloss,obvious hair loss,slow movement,like to be crowded together,and unresponsive.Some rats appear irritable,aggressive and irritable..Some rats were irritable,aggressive and irritable.Compared with model group,estradiol valerate group and Chaihu Siwu decoction high-dose,medium-dose and low-dose groups showed more symmetrical body shape,better hair gloss,slight shedding,increased activity,more sensitive response,less irritability,aggression,irritability and other phenomena.Compared with estradiol valerate group,there was no significant difference in appearance signs in Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups.(2)Changes in body weight:On the 7th,14th,21st,and 28th day of drug intervention,compared with the sham operation group,the body weight of the model group increased significantly(P<0.01).Compared with model group,body weight of estradiol valerate group,Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was decreased to a certain extent,and the difference was statistically significant(P<0.05 or P<0.01).Compared with estradiol valerate group,there was no statistical significance in body weight of Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups(P>0.05).(3)Changes in food intake:Compared with the sham operation group,food intake in the model group was significantly increased on the 7th,14th,21st,and 28th day of intervention(P<0.01).Compared with model group,the food intake of estradiol valerate group,Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was reduced to a certain extent,with statistical significance(P<0.05 or P<0.01).Compared with estradiol valerate group,there was no statistical significance in food intake of Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups(P>0.05).(4)Changes in water intake:On the 7th,14th,21st,and 28th day of intervention,compared with the sham operation group,the drinking water volume of the model group was significantly increased(P<0.05 or0.01).Compared with model group,the water intake of estradiol valerate group,Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was reduced to a certain extent,with statistical significance(P<0.05 or P<0.01).Compared with estradiol valerate group,there was no statistical significance in drinking water quantity of Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups(P>0.05).(5)Changes in activities:Compared with the sham operation group,the total movement distance in the model group was significantly reduced,and the difference was statistically significant(P<0.01).Compared with model group,the total movement distance of estradiol valerate group,Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly increased,with statistical significance(P<0.01).Compared with the Estradiol Valerate group,the total movement distance of Chaihu Siwu Decoction high-dose and medium-dose groups was relatively small,but the difference was not statistically significant(P>0.05),while the total movement distance of Chaihu Siwu Decoction low-dose group was significantly less than that of the Estradiol Valerate group,the difference was statistically significant(P<0.01).Compared with the sham operation group,the activity time in the model group was decreased and the rest time was increased,with statistically significant differences(P<0.01).Compared with model group,activity time increased and rest time decreased in estradiol valerate group and Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups,with statistically significant differences(P<0.05 or P<0.01).Compared with estradiol valerate group,the activity time of Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was relatively decreased,while the rest time was relatively increased,but there was no statistical significance(P>0.05).Experiment 2:Effects of Chaihu Siwu Decoction on uterine index,pathological changes and ER?in perimenopausal syndrome model rats(1)Changes in uterine index:Compared with sham operation group,uterine wet weight and uterine index in model group were significantly decreased,with statistical significance(P<0.01).Compared with model group,estradiol valerate group,radix b Chaihu Siwu decoction of high,medium and low dose group of the uterus index increased significantly,the difference is statistically significant(P<0.01),but in terms of wet weight of uterus,estradiol valerate group of uterine wet weight increases slightly,statistically significant difference(P<0.05)and radix Chaihu Siwu decoction high,medium and low dose group of wet weight of uterus,although a slight increase,But there was no statistical significance(P>0.05).Compared with estradiol valerate group,there were no significant differences in uterine wet weight and uterine index in Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups(P>0.05).(2)Changes in uterine morphology:Compared with sham operation group,the uterine volume of model group was significantly reduced,uterine cavity was narrowed,endometrial epithelial cells were flattened,irregularly arranged,and some of them had defects,the number of uterine glands in lamina propria was less,and endometrial and myometrium were obviously atrophied.Compared with model group,the number of uterus glands in estradiol valerate group,Chaihu Siwu decoction high-dose,medium-dose and low-dose groups increased to a certain extent,and the atrophy of endometrium and myometrium was improved to a certain extent.Compared with estradiol valerate group,there was no significant difference in the number of uterine glands,endometrium and myometrium atrophy in Chaihu Siwu decoction high-dose,medium-dose and low-dose groups.(3)Changes of ER?in uterus:Compared with sham operation group,the relative expression level of ER?m RNA in uterus of model group was significantly decreased,and the difference was statistically significant(P<0.01).Compared with model group,the relative expression level of ER?m RNA in uterus of estradiol valerate group and Chaihu Siwu Decoction high-dose and medium-dose groups was significantly increased(P<0.01),while the relative expression level of ER?m RNA in uterus of Chaihu Siwu Decoction low-dose group was slightly increased,but there was no significant difference(P>0.05).Compared with the Estradiol Valerate group,the uterine ER?m RNA of Chaihu Siwu Decoction high-dose group was relatively lower,but the difference was not statistically significant(P>0.05),while the uterine ER?m RNA of Chaihu Siwu Decoction medium-dose and low-dose groups was relatively lower,the difference was statistically significant(P<0.01).The Estradiol Valerate group was superior to the Estradiol Valerate group.Compared with sham operation group,the relative expression level of ER?protein in uterus of model group was significantly decreased,and the difference was statistically significant(P<0.01).Compared with model group,the relative expression level of uterine ER?protein in estradiol valerate group and Chaihu Siwu Decoction high-dose group increased significantly,the difference was statistically significant(P<0.01),while the relative expression level of uterine ER?protein in Chaihu Siwu Decoction medium-dose and low-dose groups increased slightly,but the difference was not statistically significant(P>0.05).Compared with estradiol valerate group,the relative expression level of ER?protein in uterus of Chaihu Siwu Decoction high-dose group was lower,but the difference was not statistically significant(P>0.05),while the relative expression level of ER?protein in uterus of Chaihu Siwu Decoction medium-dose and low-dose groups was significantly lower,the difference was statistically significant(P<0.01).Estradiol valerate group is superior to chaihu Siwu decoction medium and low dose groups.Experiment 3:Effects of Chaihu Siwu Decoction on the levels of E2,FSH,LH in serum and FSH,LH in pituitary homogenate in perimenopausal syndrome model rats(1)Changes of E2 level in serum:Compared with sham operation group,the E2 level in serum of model group was significantly decreased,with statistical significance(P<0.01).Compared with model group,the E2 level in serum of estradiol valerate group and Chaihu Siwu Decoction high-dose and medium-dose groups was significantly increased(P<0.01),while the level of E2 in serum of Chaihu Siwu Decoction low-dose group was also increased to a certain extent,but the difference was not statistically significant(P>0.05).Compared with the Estradiol Valerate group,the E2 level in serum of the high dose group of Chaihu Siwu Decoction was lower,but the difference was not statistically significant(P>0.05),the E2 level in serum of the middle dose group of Chaihu Siwu Decoction(P<0.05)and the low dose group of Chaihu Siwu Decoction(P<0.01)was lower,the difference was statistically significant,and the Estradiol Valerate group was better than the middle and low dose groups of Chaihu Siwu Decoction.(2)Changes of FSH level in serum and pituitary:Compared with sham operation group,FSH level in serum of model group was significantly increased,the difference was statistically significant(P<0.01).Compared with model group,FSH level in serum of estradiol valerate group and Chaihu Siwu Decoction high-dose and medium-dose groups was significantly decreased(P<0.01),and FSH level in serum of Chaihu Siwu Decoction low-dose group was slightly decreased(P<0.05),the difference was statistically significant;Compared with the Estradiol Valerate group,the FSH level in serum of chaihu Siwu Decoction high-dose group was higher,but the difference was not statistically significant(P>0.05);the FSH in serum level of Chaihu Siwu Decoction medium-dose and low-dose groups was higher,and the difference was statistically significant(P<0.01).The Estradiol Valerate group was superior to the Estradiol Valerate group.Compared with sham operation group,the FSH level in pituitary of model group was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,the FSH level in pituitary of estradiol valerate group and Chaihu Siwu Decoction high-dose and medium-dose groups was significantly decreased(P<0.01),and the difference was statistically significant;the FSH level in pituitary of chaihu Siwu Decoction low-dose group was slightly decreased(P>0.05),and the difference was not statistically significant.Compared with the Estradiol Valerate group,the FSH level in pituitary of the high-dose group of Chaihu Siwu Decoction was higher,but the difference was not statistically significant(P>0.05);the FSH level in pituitary of the medium-dose and low-dose groups of Chaihu Siwu Decoction was higher,and the difference was statistically significant(P<0.01).(3)Changes of LH level in serum and pituitary:Compared with sham operation group,the LH level in serum of model group was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,the LH level in serum of estradiol valerate group,chaihu Siwu Decoction high-dose,medium-dose and low-dose groups were significantly decreased(P<0.01),and the difference was statistically significant.Compared with the estradiol valerate group,the LH level in serum of the high-dose chaihu Siwu Decoction group was higher,but the difference was not statistically significant(P>0.05);the LH level in serum of the medium and low-dose Chaihu Siwu Decoction groups was higher,and the difference was statistically significant(P<0.01).Compared with sham operation group,the LH level in pituitary of model group was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,the LH level in pituitary of estradiol valerate group,chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased(P<0.01),and the difference was statistically significant.Compared with the Estradiol Valerate group,the LH level in pituitary of the high-dose chaihu Siwu Decoction group was higher,but the difference was not statistically significant(P>0.05);the LH level in pituitary of the medium and low-dose Chaihu Siwu Decoction groups was higher,and the difference was statistically significant(P<0.01).The Estradiol Valerate group was superior to the medium and low-dose Chaihu Siwu Decoction groups.Experiment 4:Effects of Chaihu Siwu Decoction on pituitary Gn RH-R in perimenopausal syndrome model ratsCompared with sham operation group,the relative expression level of Gn RH-R m RNA in pituitary of model group was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,Gn RH-R m RNA relative expression level of pituitary in estradiol valerate group,Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased(P<0.01),and the difference was statistically significant.Compared with the Estradiol Valerate group,the pituitary Gn RH-R m RNA relative expression level of Chaihu Siwu Decoction high-dose group was higher,but the difference was not statistically significant(P>0.05);the pituitary Gn RH-R m RNA relative expression level of Chaihu Siwu Decoction medium-dose and low-dose groups was higher,and the difference was statistically significant(P<0.01).Estradiol valerate group is superior to Chaihu Siwu decoction medium and low dose groups.Compared with sham operation group,the relative expression level of pituitary Gn RH-R protein in model group was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,the relative expression level of pituitary Gn RH-R protein in estradiol valerate group,Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased(P<0.05 or P<0.01),and the difference was statistically significant.Compared with the Estradiol Valerate group,the relative expression level of pituitary Gn RH-R protein was higher in the high,medium and low dose groups of Chaihu Siwu Decoction,and the difference was statistically significant(P<0.05 or P<0.01).The Estradiol Valerate group was superior to the high,medium and low dose groups of Chaihu Siwu Decoction.Experiment 5:Effect of Chaihu Siwu Decoction on Gn RH in ARC region of hypothalamus in perimenopausal syndrome model ratsCompared with sham operation group,the relative expression level of Gn RH m RNA in ARC region of hypothalamus in model group,Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly increased,with statistical significance(P<0.01).Compared with model group,the relative expression level of Gn RH m RNA in ARC region of hypothalamus in estradiol valerate group and Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased,with statistical significance(P<0.01).Compared with the Estradiol Valerate group,the relative expression level of Gn RH m RNA in ARC region of hypothalamus in the high-dose group was higher than that in the Estradiol Valerate group,but the difference was not statistically significant(P>0.05);the relative expression level of Gn RH m RNA in ARC region of hypothalamus in the middle-dose and low-dose groups was higher than that in the Estradiol Valerate group,and the difference was statistically significant(P<0.01).Compared with sham operation group,the relative expression level of Gn RH in ARC region of hypothalamus in model group,Chaihu Siwu Decoction medium and low dose groups was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,the relative expression level of Gn RH in ARC region of hypothalamus in estradiol valerate group and Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased,with statistical significance(P<0.01).Compared with the Estradiol Valerate group,the relative expression level of Gn RH protein in ARC region of hypothalamus of Chaihu Siwu Decoction high-dose group was slightly higher,but the difference was not statistically significant(P>0.05);the relative expression level of Gn RH in ARC region of hypothalamus of Chaihu Siwu Decoction middle-dose and low-dose groups was higher,and the difference was statistically significant(P<0.01).Experiment 6:Effects of Chaihu Siwu Decoction on Kisspeptin,GPR54and ER?in ARC region of hypothalamus in perimenopausal syndrome model ratsCompared with sham operation group,the relative expression level of KISS-1 m RNA in ARC region of hypothalamus in model group was significantly increased,with statistical significance(P<0.05 or P<0.01).Compared with model group,the relative expression level of KISS-1m RNA in ARC region of hypothalamus in estradiol valerate group and Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased,with statistical significance(P<0.01).Compared with the Estradiol Valerate group,the relative expression level of KISS-1 m RNA in ARC region of hypothalamus of Chaihu Siwu Decoction high-dose group was higher,but the difference was not statistically significant(P>0.05);the relative expression level of KISS-1 m RNA in ARC region of hypothalamus of Chaihu Siwu Decoction medium-dose and low-dose groups was higher,and the difference was statistically significant(P<0.01).Estradiol valerate group is superior to chaihu Siwu decoction medium and low dose groups.Compared with sham operation group,the relative expression level of Kisspeptin in ARC region of hypothalamus in model group was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,the relative expression level of Kisspeptin in ARC region of hypothalamus in estradiol valerate group,Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased,with statistical significance(P<0.01).Compared with estradiol valerate group,the relative expression level of Kisspeptin in ARC region of hypothalamus in Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was higher,but the difference was not statistically significant(P>0.05).Compared with sham operation group,the relative expression level of GPR54 m RNA in ARC region of hypothalamus in model group was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,the relative expression level of GPR54m RNA in ARC region of hypothalamus in estradiol valerate group and Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased,with statistical significance(P<0.01).Compared with the Estradiol Valerate group,the relative expression level of GPR54 m RNA in ARC region of hypothalamus in the high,medium and low dose chaihu Siwu Decoction groups was higher,the difference was statistically significant(P<0.01),and the Estradiol Valerate group was superior to the high,medium and low dose Chaihu Siwu Decoction groups.Compared with sham operation group,the relative expression level of GPR54 in ARC region of hypothalamus in model group was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,the relative expression level of GPR54 in ARC region of hypothalamus in estradiol valerate group and Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased,with statistical significance(P<0.05 or P<0.01).Compared with the Estradiol Valerate group,the relative expression level of GPR54 in ARC region of hypothalamus of Chaihu Siwu Decoction high-dose group was higher,but the difference was not statistically significant(P>0.05).The relative expression level of GPR54 in ARC region of hypothalamus of Chaihu Siwu Decoction medium-dose and low-dose groups was increased.The difference was statistically significant(P<0.05or P<0.01),and the Estradiol Valerate group was superior to the chaihu Siwu Decoction medium-dose and low-dose groups.Compared with sham operation group,the relative expression level of ER?m RNA in ARC region of hypothalamus in model group was significantly increased,the difference was statistically significant(P<0.01).Compared with model group,the relative expression level of ER?m RNA in ARC region of hypothalamus in estradiol valerate group and Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased,and the difference was statistically significant(P<0.01).Compared with the Estradiol Valerate group,the m RNA relative expression level of ER?in ARC region of hypothalamus of Chaihu Siwu Decoction high-dose group was higher,but the difference was not statistically significant(P>0.05),while the relative expression level of ER?m RNA in ARC region of hypothalamus of Chaihu Siwu Decoction medium-dose and low-dose groups was higher,and the difference was statistically significant(P<0.01).Estradiol valerate group is superior to chaihu Siwu decoction medium and low dose groups.Compared with sham operation group,the relative expression level of ER?in ARC region of hypothalamus in model group was significantly increased,and the difference was statistically significant(P<0.01).Compared with model group,the relative expression level of ER?in ARC region of hypothalamus in estradiol valerate group and Chaihu Siwu Decoction high-dose,medium-dose and low-dose groups was significantly decreased,and the difference was statistically significant(P<0.01).Compared with the Estradiol Valerate group,the relative expression level of ER?in ARC region of hypothalamus in Chaihu Siwu Decoction high-dose and medium-dose groups was higher,but the difference was not statistically significant(P>0.05),while the relative expression level of ER?in ARC region of hypothalamus in Chaihu Siwu Decoction low-dose group was increased,the difference was statistically significant(P<0.01).The Estradiol Valerate group was superior to the low dose Chaihu Siwu decoction group.Conclusion:(1)The records of perimenopausal syndrome in ancient books are mainly found in"hysterian","lily disease","menorrhagia in middle-aged and elderly","postmenopausal menstruation","depression syndrome","insomnia","palpitation","fatigue"and so on.Clearly recorded perimenopausal women of the disease is the most"irregular vaginal bleeding",other diseases are scattered in the medical literature.(2)Professor Mei Guoqiang believes that the pathogenesis of perimenopausal syndrome mainly includes the following three aspects:(1)Chong and Ren Channel deficiency,Yin and Yang imbalance;(2)Shaoyang Gallbladder Channel of Foot stasis and fire rushing;(3)Shaoyang Sanjiao Channel of Hand is unfavorable,phlegm dampness or damp heat inside.Chaihu Siwu Decoction has the functions of operating the cardinal,clearing the fire,cooling blood and calming the liver,etc.It takes into account the two systems of Shaoyang Channel,Chong and Ren Channel,and relieve various symptoms of perimenopausal syndrome.(3)Chaihu Siwu Decoction can effectively reduce the body weight,food intake,water intake and increase the activities of the perimenopause syndrome model rats.It can effectively reduce the obesity of the perimenopause syndrome model rats.(4)Chaihu Siwu Decoction can effectively increase the uterine weight,uterine index and increase the expression of ER?in uterine of the perimenopause syndrome model rats.It can effectively relieve uterine atrophy.(5)Chaihu Siwu Decoction can increase the level of E2 in serum,decrease the levels of FSH,LH in serum and pituitary of the perimenopause syndrome model rats.Chaihu Siwu Decoction can down-regulate the expression of Gn RH-R in pituitary,and down-regulate the expression of the ER?,Kisspeptin,GPR54,Gn RH in ARC region of hypothalamus in the perimenopause syndrome model rats.Chaihu Siwu Decoction can improve the HPO axis homeostasis of perimenopausal syndrome model rats through the different ways,and play a significant role in regulating the secretion of hormones. |
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