Study On Mechanism Of Anti-mammary Gland Hyperplasia Of Xihuang Pill

Objective:To investigate the impacts on related hormones and receptors,microenviron-ment and serum biochemical index of rats with mammary gland hyperplasia by Xihuang Pills,to explore Xihuang Pills’s inhibition mechanism on mammary gland hyperplasia,and to provide theoretical foundation for the clinical about preventing breast hyperplasia.Methods:Ninety Wistar rats were randomly divided into six groups:blank group,model group,positive control group,high,middle and low dose groups of Xihuang Pill.Established rats model of mammary hyperplasia by intramuscular injection estradiol benzoate 0.5 mg/kg and progestin 5 mg/kg,while blank group were injected with saline 0.05 ml per day.Blank and model groups were given distilled water,positive control group were given tamoxifen0.0018 g/kg and Drug groups were given correspond medicines（2.16 g/kg,1.08 g/kg,0.54 g/kg）from first modeling day to 31st day once per day.Rat nipple diameter and height was examined by vernier calipers;the organ indexes（thymus,spleen）were calculated;the levels of E2,P,PRL,T,IL-2 and TNF-αin the serum of rats were measured by ELISA;SOD activity and MDA content were calculated by chemistry kit;Semi-quantitative analysis for the expression of ERαand ERβ,PR,VEGF,bFGF and PCNA in mammary tissue were measured by immunohistochemical methodResult:1.Form nipple diameter and height,and mammary histopathology,comparedwith the model group,the nipple diameters of the rats in the high,middle and low dose groups of Xihuang Pill were significantly reduced（P<0.01）;the height of rat nipples in Xihuang Pill high and middle dose group was significantly reduced（P<0.01 or P<0.05）,and the nipple height in low dose group of Xihuang Pill had a decreasing trend,the difference was not statistically significant（P>0.05）.The results of HE staining showed that there was no hyperplasia of mammary glands in the blank group;in the model group,the number of mammary glands and acini in the mammary glands increased,the acinar cavities expanded significantly,and the epithelial cells proliferated;after Xihuang Pill intervention,the number of breast lobules and acini decreased,acinar began to shrink,cavity secretions also decreased,and the proliferation was improved.It can be detected by stereo quantification method,compared with the model group,the lobular body density and acinar specific surface area decreased,and interstitial density increased of the rats in the high,middle,and low dose groups of Xihuang Pill（P<0.01 or P<0.05）.2.From the content of serum hormone and the expression level of mammary gland receptor,compared with the model group,the levels of serum E₂,PRL,and T of Xihuang Pill high,middle,and low dose groups were decreased,and the P level was increased（P<0.01 or P<0.05）;the expression of ERαand PR in the breast tissue of Xihuang Pill high,middle,and low dose groups was weakened（P<0.01 or P<0.05）,there was no difference in the expression of ERβ（P>0.05）.3.From the microenvironment,compared with the model group,the blood viscosity and plasma viscosity of Xihuang Pill high,middle,and low dose groups were decreased（P<0.01or P<0.05）,and the low-cut whole blood viscosity of Xihuang Pill low dose group had a decreasing trend,the difference was not statistically significant（P>0.05）;the expression of VEGF,bFGF,and PCNA in the mammary glands of Xihuang Pill high,middle,and low dose groups was weakened（P<0.01 or P<0.05）,the PCNA expression of Xihuang Pill low dose group had a tendency to decrease,the difference was not statistically significant.（P>0.05）.4.From the serum biochemical indicators,compared with the model group,the IL-2content of Xihuang Pill high,middle,and low dose groups were increased（P<0.01 or P<0.05）,and TNF-αcontent decreased.（P<0.01 or P<0.05）;the SOD activity of Xihuang Pill high,middle and low dose groups was increased（P<0.01 or P<0.05）,while MDA content decreased（P<0.01）.Conclusion:1.Xihuang Pill can reduce the diameter and height of nipple and improve the pathological changes of mammary gland hyperplasia,and has the effect of anti-mammary gland hyperplasia,the mechanism is mainly to reduce the content of E₂,PRL and T,increase the content of P,and to reduce the expression of ERαand PR in mammary gland tissue,regulate hormonal disorders and reduce receptor sensitivity.2.Xihuang Pill can reduce the blood viscosity of mammary gland hyperplasia rats,reduce the expression of VEGF,bFGF and PCNA in mammary gland tissue,inhibit the neovascularization and epithelial cell proliferation;increase thymus and spleen organ index,IL-2 content,decrease TNF-αcontent,enhance the immune clearance function;enhance SOD activity,reduce MDA content,inhibit lipid peroxidation,regulate free radical metabolism.3.Xihuang Pill can not only regulate the expression of hormones and receptors,but also improve the microenvironment,enhance immune function and anti-oxidation ability.It shows that Xihuang Pill has anti-breast hyperplasia effect and is a multi-link and multi-target.