Mechanisms Of Chaiyu Dixian Prescription Combined With Metformin On Polycystic Ovarian Syndrome Complicated With Depression In Rats

Objective:1.Observe the effects of dehydroepiandrosterone-induced polycystic ovary syndrome in rats on behavior,neuroendocrine changes and chronic restraint stress on polycystic animals,and to explore the mechanism of polycystic ovary syndrome complicated with depression and the effects of environmental stimulation on polycystic ovary syndrome.2.Compare the pharmacological effects of Chaiyu Dixianfang,metformin and their combination therapy on rats with polycystic ovary syndrome complicated with depression,and to explore their mechanism from the aspects of HPO axis,androgen levels,insulin levels and monoamine neurotransmitter function.Method:A model of polycystic ovary syndrome was induced by subcutaneous injection of dehydroepiandrosterone in female rats.Based on that,28-day chronic restraint stress was simultaneously administered,and a rat model of polycystic ovary syndrome complicated with depression was replicated.The experimental animals were divided into control group,PCOS group,model group,Chaiyu Dixianfang group,metformin group and combination treatment group.The estrous cycle and behavioral changes of rats were evaluated by observation of vaginal exfoliated cells,body mass,open field movement path,immobile time in Forced Swim Test(FST)and Tail Suspension Test(TST).The contents of serum GnRH,LH,FSH,E2,T,A2,INS,and 5-HT,NE,DA in hypothalamus and hippocampus were detected by ELISA.The morphology of ovary and the development of follicles were observed by HE staining.Results:1.Compared with the control group:the PCOS group and the model group rat’s horizontal movement distance,the number of uprights,the central area residence time,the ratio of central area horizontal movement distance and the number of entering the central area decreased,the number of excretions increased,and the immobile time in FST and TST increased;the proportion of early antral follicles and corporal lutea in ovaries decreased,as well as the proportion of atresia follicles increased,and cystic follicles appeared;the contents of DA and 5-HT in hypothalamus and hippocampus decreased,and NE contents increased;the serum GnRH,LH,T,A2,INS contents increased and FSH,E2 contents decreased;the PCOS group rat’s body mass increased(P<0.01).Compared with the PCOS group,the model group rat’s body mass decreased,and the insulin levels increased(P<0.01).2.Chaiyu Dixianfang could improve the behavior in the model group,regulate the contents of 5-HT,DA and NE in the hypothalamus and hippocampus,stabilize the secretion of GnRH and LH,up-regulate serum E2 and FSH levels,decrease androgen and insulin levels,and improves the developmen of ovarian follicles(P<0.05,P<0.01).3.Metformin could improve the horizontal movement distance and the number of uprights in the model group,reduce the number of excretions and the immobile time of FST and TST,regulate the contents of 5-HT,DA and NE in the hypothalamus and hippocampus,and stabilize the secretion of GnRH and LH.The serum E2 and FSH levels were up-regulated,and the levels of androgen and insulin were decreased,and the development of follicular was improved(P<0.05,P<0.01).4.The combination of Chaiyu Dixianfang and metformin could improve the function of HPO axis in the model group,reduce hyperandrogenism,hyperinsulinemia,improve behavior,central monoamine neurotransmitter function,and regulate follicular development,especially in regulation the contents of hypothalamus 5-HT.hippocampal NE and serum T levels(P<0.05,P<0.01).Conclusion:1.Dehydroepiandrosterone can induce polycystic ovary syndrome in rats,affecting neuroendocrine function and causing depression-like behavior,suggesting that the depression of polycystic ovary syndrome may originate from autonomic neuroendocrine dysfunction,and chronic stress may aggravate hyperinsulinemia in polycystic ovary syndrome.2.Chaiyu Dixianfang can improve the spontaneous activity,the desire to explore,the negative,desperate behavior and nervousness,anxiety of the polycystic ovary syndrome complicated with depression rats;the mechanism is related to the regulation of central monoamine neurotransmitter function.The follicular development in model rats is related to its’stabilization of HPO axis and the reduction of androgen and insulin levels.3.Metformin can improve the ability of spontaneous activity,the desire to explore,and negative,desperate behavior,and improve follicular development in model rats of polycystic ovary syndrome complicated with depression.Achieving the effect may be through regulating central monoamine neurotransmitter levels,HPO axis function and decreasing the androgen and insulin levels4.The combination of Chaiyu Dixianfang and metformin has a synergistic effect on improving the symptoms of polycystic ovary syndrome complicated with depression.