Experimental Study Of Anti-estrogen Therapies For Benign Prostatic Hyperplasia

Objective:Hyperplasia of stroma is of importance to prostatic hyperplasia. Estrogen plays an important role in the stroma hyperplasia. The experiment is aiming to approach the effect of two anti-estrogen medicines in hyperplasic prostatic stroma cells and in hyperplasia model of male rats, expecting to offer a new route for curing BPH.Methods:Human being prostatic stroma cells CRL2854were stimulated by estrogen, meanwhile,4OH-tamoxifen and raloxifen was used to antagonize the effect of estrogen. subsequently, detect the cell proliferation by MTT; Estrogen and androgen with ratio of1:100induced the castrated rats to establish the model of hyperplasic prostatic stroma; The low, middle and high dose of tamoxifen and raloxifen were applied to the rats, Prostate tissue was pathologically stained with HE,1) Observe the epithelium and stroma.2) measure the thickness of smooth muscle in stroma with the scale in onside eyelens of microscape.Results:1.Reusult of cell experiment:1) Compared to the group which was simply stimulated by estrogen, the optical density of every concentration of raloxifen can antagonize the effect of estrogen on proliferation of prostatic stroma. And there was no difference between3concentrations of raloxifen in inhibiting estrogen from promoting the cell proliferation of prostatic stroma cells.2) In the comparison between every concentration of tamoxifen and estrogen, only high-dose group can antagonize the effect of estrogen. And the effect was different between the3concentrations of4OHT group. Compared to the other two groups including low and middle dose groups, the OD of high-dose group was different in the effect.2. Result of animal experiment:Pathological section to the prostate of mouse:1) Epithelial cells of normal group displayed cubic and high columnar; the content of stroma was very few, there was not obvious hyperplasic smooth muscle and fibrous tissue.2) The gland of model group was low-grade hyperplasia; the smooth muscle around the gland was thickest and the fibrous tissue increased in all these groups.3) The epithelial cells of every concentration of finasteride displayed cubic and high columnar with some acinus disintegration; same changes happened with model group in the stroma.4) There were same changes to the epithelium of the every concentration of tamoxifen; the smooth muscle around gland of middle and high dose group was thinner than low dose group.5) There were same changes to the epithelium of the every concentration of raloxifen; the smooth muscle around gland of middle and high dose group was thinner than low dose group.6) The changes of epithelium in mixture group lied between the normal and model group; the smooth muscle was thinner and the fibrous tissue was hardly found.Calculate the thickness of smooth muscle in stroma.1) Comparing the thickness of smooth muscle around gland between normal group and model group, the result was statistical different.2) Comparing the thickness of smooth muscle around gland between normal group and every concentration of all these groups of raloxifen, finasteride, raloxifen and mixture, the result was statistical different.3) Comparing the thickness of smooth muscle around gland between model group and every concentration of all these groups of raloxifen, finasteride, raloxifen and mixture, the result was statistical different.4) The comparison between every concentration of finasteride and tamoxifen was not statistical different.5) There was statistical different between the high-dose group of raloxifen and low, middle, and high dose group of tamoxifen.6) There was not statistical different between mixture group and middle-dose group of tamoxifen; but there was statistical different between mixture group and middle-dose group of finasteride.Conclusion:1. Estrogen and androgen with the ratio of1:100can successfully induce hyperplasic animal model especial hyperplasia of stroma. The successful model proves that estrogen can promote the hyperplasia of prostate especial stroma.2. As selective estrogen receptor modulators, tamoxifen and raloxifen can antagonize the effect of estrogen, and restrain the hyperplasia of the stroma; As to the effect, raloxifen is better than tamoxifen.