Study On The Formulation Optimization And The Mechanism Of HRYZ ?

Objective:In this study,through the modern pharmacology research methods,therapeutic effect of different prescription by observing the back to add a number of dairy inhibition on hyperplasia of mammary glands and the HPRL two kind of model rats,to explore the mechanism of the drug treatment of the two diseases,thus the optimal formulation was selected,for the later be developed to provide reliable experimental basis of hospital preparations.At the same time,through the study of hyperplastic disease of the breast and hyperprolactinemia pathogenesis,to find a new method for preparation and with hyperplasia of mammary glands and hyperprolactinemia two disease animal model.Methods:The selection of female non pregnant Wistar rats,intramuscular injection of estradiol benzoate injection 0.5 mg/kg,continuous 25d,and then switch to Progesterone Injection 5 mg/kg,Im.continuous 5d,causing the model of hyperplasia of mammary glands.Were randomly divided into 15 groups,8 rats in each group,each group after modeling according to the weight of administration,in every afternoon 16:00 administration time,dosage of 1.5 ml,the normal group and model group were given distilled water capacity,for 30 consecutive days.24 hours after the last administration,the eyeball blood used in the next day.Estradiol serum using ELISA method?E2?,progesterone?P?,prolactin?PRL?,follicle stimulating hormone?FSH?,luteinizing hormone?LH?content.Section of rats in each group the breast tissue,conventional production,after HE staining to observe the morphological changes of breast tissue in rats of each group under the microscope,including acinar,ductal lobular hyperplasia,the shape and thickness and whether the discharge.The selection of female non pregnant Wistar rats,intramuscular injection of estradiol benzoate injection 0.5mg/kg,continuous 25d,and then switch to Progesterone Injection 5mg/kg,Im,continuous 5d,causing the model of hyperplasia of mammary glands.Were randomly divided into 15 groups,8 rats in each group,each group after modeling according to the weight of administration,in every afternoon 16:00 administration time,dosage of 1.5 ml,the normal group and model group were given distilled water capacity,for 30 consecutive days.24 hours after the last administration,the eyeball blood used in the next day.Estradiol serum using ELISA method?E2?,progesterone?P?,prolactin?PRL?,follicle stimulating hormone?FSH?,luteinizing hormone?LH?content.Section of rats in each group the breast tissue,conventional production,after HE staining to observe the morphological changes of breast tissue in rats of each group under the microscope,including acinar,ductal lobular hyperplasia,the shape and thickness and whether the discharge.The selection of female Wistar rats,were randomly divided into 3groups:normal group,model group A,model group B.Model group A rats were injected with Estradiol Benzoate Injection 0.5mg/kg,continuous25d,and then switch to Progesterone Injection 5 mg/kg,for 5 consecutive days,then subcutaneous injection of metoclopramide 50mg/kg,continuous10d.ModelBratsbysubcutaneousinjectionof metoclopramidehydrochloride50mg/kg,continuous10d,and intramuscularinjectionEstradiolBenzoateInjection0.5mg/kg,continuous 25d,and then switch to Progesterone Injection 5 mg/kg,for 5consecutive days.The rats in the last Administration for first days,seventh days,fourteenth days,twenty-eighth days of using angular vein blood sampling.Application of ELISA method,PCR and Western blot technology in the detection of the serum levels of estradiol?E2?,progesterone?P?,prolactin?PRL?content.Section of rats in each group the breast tissue,conventional production,after HE staining to observe the morphological changes of breast tissue in rats of each group under the microscope,including acinar,ductal lobular hyperplasia,the shape and thickness and whether the discharge.The selection of female Wistar rats,were randomly divided into 7groups,8 rats in each group.In addition to the normal rats,the remaining rats were subcutaneous injection of metoclopramide 50 mg/kg,continuous 10d,and intramuscular injection Estradiol Benzoate Injection0.5mg/kg,continuous 25d,and then switch to Progesterone Injection 5mg/kg,for 5 consecutive days.After modeling according to the weight of each administration,in every afternoon 16:00 administration time,dosage of 1.5 ml,the normal group and model group were given distilled water capacity,for 30 consecutive days.24 hours after the last administration,the eyeball blood used in the next day.Estradiol serum using ELISA method?E₂?,progesterone?P?,prolactin?PRL?,follicle stimulating hormone?FSH?,luteinizing hormone?LH?content.Section of rats in each group the breast tissue,conventional production,after HE staining to observe the morphological changes of breast tissue in rats of each group under the microscope,including acinar,ductal lobular hyperplasia,the shape and thickness and whether the discharge.Results:Compared with the normal group,the increase of E₂,PRL content in serum of the rats in the model group,decreased the content of P in serum,breast tissue pathology showed four level in rats with hyperplasia of mammary glands hyperplasia,proved that the model was established successfully.Compared with the model group,the serum hormone group rats in each treatment values were lower?P<0.05?;compared with the other groups,formula 8 were decreased in rats serum estradiol?P<0.05?,prolactin?P<0.05?,follicle stimulating hormone?P<0.05?,improve the progesterone?P<0.05?,luteinizing hormone?P<0.05?acinar secretion;significantly reduce the number and the number of breast lobule,lobular,treat the effect best,presumably for the optimal prescription.Compared with the normal group,the PRL content in serum of the rats in the model group increased significantly?E2?P content in serum decreased significantly,proved that the rat model of hyperprolactinemia establishment success.Compared with the model group,the serum hormone PRL rats in each treatment values were lower?P<0.05?;compared with the other groups,formula 8 significantly decreased the contents of serum lactation rats element?P<0.05?,treat the effect best,which is determined as the optimal prescription.Compared with the normal group,model group B rats after the completionof gradethreehyperplasia,and at30d,thethird grade hyperplasi a stillexisted;themodel is completed,comparedwith the normal group,model groupB inrat,thecontentofPRL increaseddramatically?P<0.01?,alt hough later reduced,but tends to be stable at 30d,and there is still much higher than normal?P<0.01?.The content of E2 increased firstly and then decreased,the content of P increased first and then decreased;PCR results showed that,PRL gene of rats was significantly higher than that in normal group;WBresultsshowed that rats,expression of PRL protein was higher than normal group.Compared with the normal group,the PRL content in serum of the rats in the model group increased significantly,compared with the blank model group,whole group,optimization of Party group,addiction has PRL content up,bromocriptine group in serum of rats decreased,among them,the most obvious effect of optimized group,were similar to the normal group;at the same time,histological results showed that the rats in the model group obviously breast lobular hyperplasia,acinar and ductal dilatation,acinar and duct internal secretion,three grade hyperplasia.Bromocriptine group rats was three grade hyperplasia,whole group,addiction groups are a hyperplasia,optimize group recovered to normal.Comprehensive serum hormone results and pathological tissue section results can conclude that optimization significantly in treating hyperplasia of mammary glands in rats with hyperprolactinemia mixed disease.Conclusion:Prescription:XiaKucao,oyster,RadixScrophulariae,ZheFritillaria,mount ainarrowhead,combination of kept,breast hprl is better than the originalparty.Prescription8:2 malt,XiaKucao,oyster,RadixScrophulariae,ZheFritillar ia,mountainarrowhead,keep apply,is superior to the effect of treatment of hyperprolactinemia primaryAt the same time,the 3 methods of using B prepared with hyperplasia of mammary glandsand hyperprolactinemia mixed model can exist stably,method of A prepared model instability.verify the prescription 8 on hyperplasia of mammary glands and HPRLdisease treatment is better than the original group.