| Objective:To further investigate the influence of external application of Chinese herbs in rat model of mammary gland hyperplasia; to detect the expression of the AP-2α,C-erbB-2 and analyzed their correlations to evaluate the role they play in the development of precancerous lesions tissues. We expect that the study will help us to elucidate the precancerous lesions mechanism and provide theoretic foundation for the external application of chinese herbs.Methods:Rat models of experimental mammary hyperplasia were established by intramuscular injection of estrogen and progestin. On this basis, syndrome of liver-qi stagnation in female rats was established by tail pinch.48 Rats were randomly divided into 8 groups:normal control group, disease model group, combination of disease and syndrome model group, the tamoxifen group, groups of high, middle and low dosage of Rupifang, and combination of disease and syndrome group of Rupifang. These groups were treated with different drugs. Observing the shape of breast, sexual hormones, pathological changes of breast tissue, and the expression level of AP-2α,C-erbB-2.Results:1. The rat body weight changes:From the second week, the body weight of rats of each experimental group all decreased to some extent, especially combination of disease and syndrome model group and combination of disease and syndrome group of Rupifang declined obviously. From the third week, the body weight of rats in treated group increased significantly. recovered to the pre-experiment level at 4 weeks except for combination of disease and syndrome group and combination of disease and syndrome group of Rupifang. Each group compared with the normal control group were different (p<0.05).2. The rat nipple height and diameter changes:Compared with the normal control group, the rat nipple height and diameter of disease model group and combination of disease and syndrome group were significantly increased (p<0.01). After drugs intervention, compared with the disease model group and combination of disease and syndrome group, the rat nipple height and diameter of each groups were significant reduced (p<0.01 or p<0.05).3. Organ Coefficient:Compared with the normal control group, the rat organ coefficients of uterus and liver of disease model group and combination of disease and syndrome group were significantly increased (p<0.01). After intervention, compared with the disease model group and combination of disease and syndrome group, uterus coefficient of rats in each group declined (p<0.01 or p<0.05).4. Sex hormone changes:Compared with the normal control group, the rat serum estradiol levels of disease model group and combination of disease and syndrome group were significantly increased and serum progesterone levels decreased significantly (p<0.01 or p<0.05). Serum estradiol of disease model group was higher than that of combination of disease and syndrome group (p<0.01). After drugs intervention, compared with the model group, serum estradiol levels of each group were significantly decreased and serum progesterone levels were significantly increased (p<0.01 or p<0.05). But serum estradiol levels of the tamoxifen group was lower than the normal control group (p<0.05).5. Histopathology changes:All the rat breast pathological tissues of disease model group and combination of disease and syndrome group were severe hyperplasia, compared with the normal control group (p<0.01). After drugs intervention, compared with the disease model group or combination of disease and syndrome group, hyperplasia of mammary glands degrees of each group decreased significantly (p<0.01).6. C-erbB-2 expression changes:There was no C-erbB-2 expression in the normal control group. model groups were significantly increased (p<0.01). Compared with the disease model group, combination of disease and syndrome group were more severe (p<0.01). After drugs intervention, compared with the model group, the C-erbB-2 expression of each group decreased significantly (p<0.01 or p<0.05). C-erbB-2 significantly increased with increasing hyperplasia degree of rat breast, C-erbB-2 expression was positively related with the hyperplasia degree of rat breast (p<0.01).7. AP-2αexpression changes:AP-2αwas expressed in the normal control group. model groups were significantly increased (p<0.01). After drugs intervention, compared with the disease model group or combination of disease and syndrome group, AP-2αexpression degrees of groups decreased significantly (p<0.01 or p<0.05). AP-2αsignificantly increased with increasing hyperplasia degree of rat breast, AP-2a expression was positively related with the hyperplasia degree of rat breast and the C-erbB-2 expression (p<0.01).Conclusions:1. Rat models of experimental mammary hyperplasia were successfully established by intramuscular injection of estrogen and progestin. On this basis, syndrome of liver-qi stagnation in female rats was successfully established by tail pinch.2. Rupifang has obvious therapeutic effect for a rat model with hyperplasia of mammary. The curing mechanism of Rupifang might be to reduce the level of serum estradiol and raise the level of progesterone, then it could make the balance of the blood estradiol and progesterone.3. Rupifang can decrease AP-2αand C-erbB-2 expression of rat mammary gland hyperplasia tissue. It shows that reduce C-erbB-2 expression by decrease AP-2αexpression might be one of the mechanism of prevention and treatment of hyperplasia of mammary glands. |
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