| Breast cancer is a kind of malignant tumor which is a serious threat to women’s health. Early detection, early diagnosis and early treatment of breast cancer, can not only greatly improve the cure rate in patients but also can practice breast conserving therapy and breast reconstruction, improve the quality of survival. So the treatment of precancerous lesions of breast cancer can achieve early intervention for breast cancer, and can prevent the happening of the tumor. At present the treatment of precancerous lesions of breast cancer is based on operation, how to intervence in the atypical hyperplasia rffectively, blocking its development to breast cancer, is the key to the traditional Chinese medicine in prevention and treatment of breast cancer research.Based on the guidance of the theory of toxin-blood stasis syndrome, this study established the toxin-blood stasis model of precancerous lesions in the rat. Choose Xihuang pill as drug intervention to study the mechanism of blood detoxification method treating atypical hyperplasia of breast cancer.Objective:Establish toxin-blood stasis model of precancerous breast lesions in rat and evaluate the model from the biological characterization changes, pathological changes, objective indicators such as the hemorheology changes and drugs counterevidence, etc. Then observe the regμLation and control function of blood detoxification method on the model:use Xihuang pill to intervent breast precancerous toxin-blood stasis model then explore the intervention mechanism from the pathological changes, the estrogen receptors, apoptosis related gene P53Bcl-2and index of the cell invasive and metastatic such as SDF-1/CXCR4axis and VEGF changes.Methods:75SPF SD female rats were randomLy divided into3groups:blank group15, control group15, other45rats were randomLy divided into model group15, Xihuang pill group15and TAM group15.Rats of blank group were given standard diet and lasts until the end of the ex per iment.On the first day, control group were gavaged with100mg/kg DMBA manufacturing breast precancerous lesion rat model; others were given DMBA associated with m μ Lt iple compound stress for10weeks to manufac turing tox in-blood stasis model. After10weeks blank group, model group rats were gavaged with lOmL/kg distilled water for30days, TAM and west yellow pill group rats were given corresponding drugs.To observe and recorde the biological characterization changes in rats on the first day, the end of10weeks and after the end of the gavage. All rats were killed after the end of the experiment, the abdominal cavity to take blood hemorheology change and SDF-1levels; the left side of the rats breast and surrounding skin is divided into two parts:one for pathological observation and immunohistochemical detection assay organizations such as ER, PR, P53, Bcl-2expression levels, another part of the Real-time PCR and Western blot assay tissue VEGF and CXCR4gene and protein expression.ResμLts:(1)DMBA joint10weeks mμLtiple compound stress to establish toxin-blood stasis rat model of breast precancerous disease reflecting the formation process of toxin-blood stasis.Model group rats biological characterization changes show a series of changes reflects the biological characterization of blood stasis syndrome such as visible tumor increased significantly, unsmoothed tumor surface, grey dark fur colour, dark tongue and so on; Pathological changes show model group rats is mostly of moderately-severe atypical hyperplasia, occasionally accompanied by the existence of intra-ductal carcinoma; model group rats increased blood viscosity than control group {P<0.05); model group ER, PR, Bcl-2, p53, VEGF and CXCR4indicators increased than control group(P<0.05); Detoxification circμLation method treatment disprove West Pill has a good intervention to the model. All above prove successfμLly modeled.(2)The pathological changes show, the model group based on severe ADH, occasionally accompanied by the emergence of intra-ductal carcinoma, Xihuang pill group is mostly of UDH with mild ADH and compared with TAM group no obvious difference.(3)The Xihuang pill and TAM can inhibit the expression of ER, PR, there was no statistically significant difference of the inhibitory effect between them (P>0.05); Xihuang pill and TAM can both inhibi t the express ion of p53and Bcl-2, the Xihuang pill intervention effect is more apparent, the difference was statistically significant (P<0.O5), Xihuang pill and TAM can inhibit VEGF expression and the activation of SDF-1/CXCR4signaling pathways, there was no statist ically significant difference of the intervent ion (P>0.05), but compared with blank group, the VEGF SDF-1/CXCR4expression is higher, the difference was statistically significant (P<0.05).Conclusion:combined the disease model with TCM etiology and pathogenesis modeling manufacturing breast precancerous lesion toxin-blood stasis model simμLating the pathogenesis, proved by the biological characterization of histopathological changes of rats, objective indicators such as the hemodynamic changes of blood and Xihuang pill treatment successfμL,.Xihuang pill can effectively improve the general situation of breast precancerous lesions in rats, reverse breast precancerous pathological changes, the mechanism of action of the effective prevention of breast cancer development may be as follows:through the inhibition of ER, PR expression, reverse the p53gene mutations, inhibit the cancer gene expression of Be1-2, further reduce the high expression of VEGF protein and block the SDF-1/CXCR4signaling pathways of abnormal activation, so as to achieve treatment mammary atypical hyperplasia reverse precancerous breast cancer block the occurrence and development of breast cancer. |
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