药物研究
DU Penghui;DING Hong
2007, 26(12): 1401-1405.
ABSTRACTObjectiveTo study the effect of mifepristone administered intrapeirtoneally on the rat with a model of hysteromyoma and probe into the possible pharmacological mechanisms. Methods75 female SD rats were randomly divided into 5 equal groups:① the normal control group; ② the model group; ③,④,⑤,lowdose, mediumdose and highdose mifepristone treatment groups. A model of hysteromyoma was set up in each of the rats of group 2 to group 5 by treatment of the animals with estradiol benzoate (E2) and progesterone (P). Rats of groups ③,④ and ⑤ were given each 0.56,1.12 and 2.24 mg·kg-1 of mifepristone administered intrapeirtoneally q.d. , respectively, for 12 consecutive weeks. Animals of group ① and group ② were given each an equivalent amount of 0.9% sodium chloride solution administered intraperitoneally q.d. for 12 weeks as well. Rats of all 5 groups were weighed 24 h. after the final medication. Serum concentrations of E2 and P were determined with the enzymelabelled McAb method while serum EGF (epidermal growth factor) level was measured with radioimmunoassay. The animals were then sacrificed. The general appearance of the uterus was kept under observation and the organ was weighed and the uterus coefficient of uterus weight/body weight(mg·g-1) was calculated. The expression of estrogen receptor and progestogen receptor in the hysteromyoma cells was examined with the immunochemical staining method. ResultsSerum concentration of E2, P and EGF in rats of group ② (model group) were strikingly higher than those in rats of group ① (normal control). The uterus weight , the uterus coefficient and the expression of estrogen receptor and progestogen receptor in the myoma cells were significantly increased in rats of the model group. Mifepristone administered intraperitoneally was shown to dramatically lower the serum levels of E2, P and EGF, inhibit the expression of estrogen receptors and progestogen receptors in the myoma cells. The effect was most prominent when the dose of mifepristone was 2.24 mg·kg-1·d-1. ConclusionMifepristone administered intraperitoneally was shown to exert definite therapeutic effects on the hystermyoma induced in rats. Mechanisms underlying the effects of the drug may be as follows: ① By lowering the serum levels of E2, P and the expression of their receptors in the myoma cells, the drug displayed a direct antagonistic action against the activities of progesterone and the biological function of estrogen, resulting in a striking alteration of the effects of these hormones and diminution of the size of the tumor and decrease in the weight of the uterus. ② By lowering the serum EGF level, the drug seems to inhibit the effect of EGFEGFR to stimulate the puliferation of tumor cells, leading to a reduction in the size of the tumor.
