Systematically Screening The Tradition Chinese Medicine For Treatment Of BPH And Elucidating The Potential Mechanisms

Benign prostatic hyperplasia(BPH)is one of the most common diseases of ageing men.It is associated with bothersome lower urinary tract symptoms (LUTS)that affect individual quality of life and create a significant economic burden to society.Benign prostatic hyperplasia is a nonmalignant enlargement of the prostate that is due to excessive cellular growth of both the glandular and the stromal elements of the gland.Complex stromal-epithelial interactions lead to benign prostatic hyperplasia in 50 percent of men by the age of 50 years.This process requires testicular androgens and progresses with age.Although transurethral resection of the prostate is an effective treatment for most men with symptomatic benign prostatic hyperplasia,it is by no means perfect.Approximately 20 to 25 percent of patients who undergo the operation do not have satisfactory long-term outcomes.The complications include impotence,postoperative urinary tract infection,and some degree of urinary incontinence,etc.Because of these problems,as well as the desire of many men to avoid surgery whenever possible,there has been much interest in alternative treatment.Medical Management including 5a-reductase inhibitors and a-Adrenergic Antagonists are only moderately effective in treating symptomatic benign prostatic hyperplasia and are associated with drawbacks that limit their efficacy.Currently,Phytotherapeutic Agents have received the most attention for their different mechanisms of action and few adverse effects.In this study,we conducted the systematical screening to find the tradition Chinese medicine for treatment of BPH and investigated their molecular mechanisms.This paper includes three parts:Part1 Screening the tradition Chinese medicine for treatment of BPH with serum pharmacologyObjective:To screen the herbs inhibiting cell proliferation of benign prostatic hyperplasia.Methods:MTT were used to examine the cell growth of human prostatic stromal cells after treated with different medicine;The expression of PCNA and bcl-2 at transcription level was detected by RT-PCR;A rat BPH model for assessment the role of different herbs was buit up successfully.Results:There was no significant difference between Chinese medicine and negtive control in the antiproliferative effect and the expression of PCNA and bcl-2 of prostatic strolmal cells(P＞0.05).Conclusion:The tradition chinese medicines were not found significant effect on BPH in vitro and in vivo,compared with negtive control.Part2 Curcumin inhibits growth,induces G₁ arrest and apoptosis On human prostatic stromal cells by regulating bcl-2/bax Objective:To investigate the effect of curcumin on apoptosis of human prostatic stromal cells.Methods:Different concentrations of curcumin were added into culture media system to induce apoptosis of human prostatic stromal cells.The apoptosis was detected by MTT assay,flow cytometry,RT-PCR and TUNEL method.Results:Curcumin at concentrations of 10-40μmol/l could inhibit the proliferation of human prostatic stromal cells in a dose-and time-dependent manner(P＜0.05);Characteristic apoptosis were confirmed by TUNEL;RT-PCR manifest downregulation of bcl-2/bax(P＜0.05);Cell cycle was arrested into G₁ phase by curcumin.Conclusion:Curcumin induce apoptosis on human prostatic stromal cells by downregulation of bcl-2/bax.Part3 Effect of Curcumin on expression of PCNA,Ki67,bcl-2 and bax in Rat Models of Benign Prostatic HyperplasiaObjective:To study the Effect of Curcumin on expression of PCNA,Ki67,bcl-2 and bax in rat models of Benign Prostatic Hyperplasia.Methods:Castrated SD rats were subcutaneously injected with testosterone propionate and at the same time received curcumin by intraperitoneal injection.The rats were decapitated at 60 days respectively,The weight of prostate and the prostate index wered obtained.The expression of PCNA,Ki67,bcl-2 and bax in prostate tissue were detected by using immunohistochemistry.Results:The weight of prostate and the prostate index were significant decreased by curcumin(P＜O.05).The expression of PCNA,Ki67 and bcl-2 in prostate tissues were suppressed by curcumin,the expression of bax conversely(P.＜0.05).Conclusion:Curcumin can regulate the expression of PCNA,Ki67,bcl-2 and bax to suppress BPH in rat models.