| ABSTRACTObjective:In this study, the method of hormonal intervention simulation etiology and pathology of mammary glands.By observing the rat general condition changes, changes in nipple diameter,light microscope pathological changes in breast tissue, serum hormone levels change,TNF-αand ERK,estrogen and progesterone receptor expression changes.Attempts from rat hypothalamic- pituitary- ovarian axis(HPOA) dysregulated signaling pathways affected areas and to explore the possible pathogenesis of mammary glands.In order to via the anterior, posterior cycle in treating Hyperplasia of Mammary Glands to provide a more objective test basis, and as screening dose, the theoretical basis for the development of new traditional Chinese medicines and to provide experimental evidence. Then we observe the curative effect of clinical application of this method.Methods:1.Experimental study:Selection of healthy non-pregnant female SPF level 90 SD rats,weighing 200±20g, 20 randomly selected as a control group, and the remaining 70 were modeling.Blank group was given each rat of right lower limbs intramuscular injection of physiological saline injection 0.2ml/kg·d,a total of 30 days to intervene.The rest given to each rat right lower limb muscle injection of estradiol benzoate 0.5mg/kg·d,25 days later, to the right of each lower limb muscle of rats injected progesterone injection 4.5mg / kg·d, for five days.30 days later, pick up 10 rats from model group and blank group randomly,aseptic operation wedge carve out third rats the left breast, fixed with 10% formaldehyde solution,embedded in paraffin,routine HE staining for histological observation under light microscope.Under the light microscope showed that the rats mammary gland ducts and acini obvioushyperplasia, suggesting the model is successful, i.e., mammary gland hyperplasia in rats to establish the model of success.After the success of modeling rats were divided1randomly1into16 groups: modelgroup,Xiaoyaosan group, tamoxifen group(TAM), lo w, medium, high dose group, each group were gavaged with corresponding drugs.The blank1 group and the model control group daily intragastric normal saline for 30 consecutive days.24 h after the last gavage,anesthesia femoral artery blood and serum tumor necrosis factor in rat serum detection of centrifugal(TNF-α), serum hormone E2, P, PRL, neuroendocrine factor beta endorphin. The rats were sacrificed after blood collection,removal of breast tissue on one side, the detection of extracellular signal-regulated kinase(ERK) and estrogen and progesterone receptors.2.Clinical experimental study: The test will choose some patients who meet the conditions,they will use the treatment of Shugan Qingre, Ruanjian Sanjie before menstruation,and use Bushen,Rougan, regulating Chong and Ren after menstruation.they will be treated for 8 weeks. After the end of treatment, We collect relevant information, The follow-up time is 3 months from the end of treatment.Then we can estimate the efficacy of useing cycle therapy with Chinese traditional medicine for treating hyperplasia of mammary glands.Results:1.Compared with the control group of rats, starting from 12 th on modeling, model group began gathering, hair rough, aggressive, breast symptoms such faint red color.After modeling rat lethargy, claw cool, irritable bowel, breast red, visible through the hair.After treatment of rats exhibit different degrees of improvement, increased activity, irritability, breast swelling phenomenon disappeared. No significant difference between the groups performance.2.Normal breast ductal epithelium was normal, no expansion of the lumen, less the number of acini, the surrounding tissue proportion much.Acinar proliferation of rats in the model group than the control group dense breast lobular duct dilatation catheter lumen can be seen more secretions.3.There were significant differences between the control group and the nipple diameter model group rats(P<0.05).Ig by each group before medication prescription No.1 nipple diameter,but with the model control group had no statistical difference(P>0.05);No significant difference between the treatment groups(P>0.05).There were significant differences drenched after Ⅱ Formula after each treatment group and the model group,only the high dosage group and blank control group had no statistical difference.4.With E2 as an indicator:Model group E2 and control group of rats in control group were statistically significant difference(P<0.05).The medicine was given orally after only in the traditional Chinese medicine dose group and model control group with significant difference(P<0.05).Xiaoyao group and the control group, the difference was statistically significant.With P as an indicator:There were significant differences between the control group P with model group rats(P<0.05).The medicine was given orally after only Xiaoyao Pill group and model control group withsignificant difference(P<0.05).In addition to Xiaoyao Pill group and blank control group no significant difference(P>0.05).With PRL as an indicator:Model group PRL and control group of rats in control group were statistically significant difference(P<0.05).Fed drugs to medium and high dose group with the control group, the difference was statistically significant(P<0.05).Nosignificant difference of Xiaoyao Pill and low dose group and blank control group(P>0.05).With β-EP as an indicator:There were significant differences in β-EP model with the control group of rats in the control group(P<0.05).The perfusion of drug group and model control group showed no significant differences(P<0.05).No significant difference in the tamoxifen group, Xiaoyao Pill and low dosegroup and blank control group(P>0.05).5.With TNF-α as an indicator:There were significant differences TNF-α model with the control group of rats in the control group(P<0.05).Perfusion of Xiaoyao Pill group after drug and low middle, high dose group and the model control group, the difference was statistically significant(P<0.05).No significant difference of Xiaoyao Pill and low dose group and blank control group(P>0.05).6.The expression intensity of ER, PR, ERKStained brown coarse granular cells for ER, PR, ERK expression of positive cells.The number of positive cells of model group increased as compared to the normal group.7.The clinical curative effectObserving 40 cases of patients, 23 cases were cured; 8 cases were markedly effective; 8cases were effective, 2 cases ineffective, the total effective rate was 95%.Conclusion:1.The general condition of cycle therapy improve abnormal behavior, hyperplasia of mammary glands in rats papilla diameter etc.. Its indicate that the rats of mammary gland hyperplasia has a certain improving effect.2.Periodic treatment by first focusing on soothing the lliver and clearing heat,Ruanjian Sanjie takes stopgap measure,Bushen Rougan,regulating Chong and Ren role,rats in vivohormone can restore caused by use of exogenous hormone imbalance,restore the regulation of hypothalamic pituitary ovarian axis,the comprehensive treatment of breast hyperplasia.3.The periodic therapy can reduce the content of TNF-α.It may treat mammary gland hyperplasia by its anti inflammation effect, thus reducing its possibility to develop breast cancer.4.High expression of estrogen, progesterone receptor and the incidence of hyperplasia of mammary glands related, cycle therapy can inhibit expression of estrogen and progesterone receptors, decreased sensitivity to estrogen and progesterone on target cells, so as to achievethe purpose of treating hyperplasia of mammary glands.5.Cycle therapy can decrease the expression of ERK protein in breast tissue hyperplasia of mammary glands in rats. The method by inhibiting the activation of ERK/ MAPK signalingpathway, to achieve the treatment of breast hyperplasia, which can reduce the possible to the development of breast cancer.6.Clinical curative effect of Cycle therapy in treatment of Breast Hyperplasia is remarkable.And Cycle therapy is helpful to the recovery of menstruation diseases. |
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