The Effect And Mechanism Of Quercetin For Curing Deficient-Milk Mice

Objective Postpartum hypogalactia(PH)refers to a common clinical problem for lactating women,who are unable to supply adequate milk for the infant needs.However,in recent years,PH has increased gradually,which has seriously affected the exclusive breastfeeding rate in the world.Therefore,as the primary factors affecting breastfeeding,PH urgently need to find a treatment and nursing measures to solve this clinical problem,which is of great significance to increase the exclusive breastfeeding rate.Prolactin(PRL)is an important hormone involved in milk secretion,which mainly depends on the secretion of lactation cells in the anterior pituitary.It has been proved that phytoestrogens can stimulate the proliferation of lactation cells and secretion of PRL.Quercetin,a natural compound with the most similar chemical structure with estrogen in phytoestrogens,has been proved to be low toxic and highly effective biological activity.Therefore,by establishing appropriate postnatal model of lactation mice,this study aims to explore the therapeutic effect and mechanism of quercetin on postpartum lactation mice.Method 1.6 mg/kg dose of bromocriptine was designed to be a model of postpartum lactate deficient mice and validated by comparing daily maternal lactation and litter weight.We design the different quercetin toward experimental mice,and compare their daily maternal lactation and litter weight,to select the optimal dose.In the present study,the postpartum mice within four groups,including control group,the model group and the treatment groups intragastrically administrated with normal saline,bromocriptine,bromocriptine plus 17α-ethinyl estradiol and bromocriptine plus quercetin,respectively,were used.The daily milk secretion and the growth and development of the offspring were evaluated.The extraction of the breast,the hypophysis,the liver,the kidney,the uterus and the ovary was performed on tenth days.Histological changes were observed in the breast,kidney and liver.The expression of PRL in pituitary and β-casein(Csn2)in mammary glands was detected by western blot and q-PCR.Stearoyl-CoA desaturase(SCD),fatty acid synthase(FAS)and α-lactalbumin(Lalba)in the breast tissues which are responsible for the production of lactose and galactose in the milk at the transcriptional level determined by q-PCR.Elisa kit was used to detect the concentration of PRL,follicle-stimulating hormone(FSH),luteinizing hormone(LH)in serum and breast tissue fluid.Primary cultured mouse mammary epithelial cells were cultured in vitro to observe the effects by MTT assay.Detect its effect on Prolactin Receptor(PRLR)and explore its mechanism.Result 1.6 mg/kg bromocentine could be used as the model dose for postpartum lactation mice.Quercetin had obvious improvement/curing effect on postpartum hypogalactia in milk-deficient mice,and the optimal dose was 50 mg/kg.Compared with the model group,the appearance and excisional biopsy and the index of the mammary gland were similar to the control group.And the serum of quercetin group and the PRL concentration in breast tissue were significantly improved,while the protein and gene expression level of PRL in the pituitary gland were been improve as well.Also,quercetin can improve protein and gene expression level of Csn2 in breast tissue and improve the lactose and creams related genes: the expression of SCD,FAS,Lalba.Compare the quercetin group and the control group with the liver,kidney,uterus and ovaries of relative quality comparison and case slice,FSH and LH concentration contrast,there were not statistically significant between two group.In vitro experiments proved that quercetin promotes the proliferation of mammary epithelial cells in mice,and also improves the protein and gene expression levels of PRLR.When the Akt pathway was blocked,the protein expression level of PRLR decreased significantly.Conclusion 50mg/kg of quercetin can significantly improve the lactation on postpartum hypogalactia in milk-deficient mice.Quercetin can exhibit weak estrogen-like effects,which can stimulate the secretion of the pituitary gland and release PRL,promoting the redevelopment of degraded breast tissue and increase the lactation yield.It can improve the milk quality as increase the expression of genes involved in the synthesis of milk proteins,lactose and milk fat.Quercetin has good biosafety performance.Quercetin can promote the generation of mice mammary epithelial cell proliferation.It also can increase the mice mammary epithelial cell membrane of PRLR loci,mechanism of action by activating AKT pathway that play the corresponding effect of breast cells.