摘要：
Stromal‑epithelial interaction serves a pivotal role in normal prostate growth, as well as the onset of benign prostatic hyperplasia (BPH). The present study aimed to explore the role of cyclopamine in the proliferation and apoptosis of epithelial and stromal cells in rats with BPH by blocking the Hedgehog signaling pathway. Cyclopamine (an inhibitor of the Hedgehog signaling pathway) was administered in a rat model of BPH, and the expression of Ki67 (proliferation factor) was determined by immunohistochemistry. In addition, epithelial and stromal cells were separated and cultured in order to investigate the role of cyclopamine in the progression of BPH. The expression of Hedgehog signaling pathway‑ and apoptosis‑related genes, including basic fibroblastic growth factor (b‑FGF) and transforming growth factor β (TGF‑β), was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Cell proliferation, cell cycle and apoptosis were analyzed using an MTT assay and flow cytometry. We identified upregulated Ki67 expression and activated Hedgehog signaling pathway in rats with BPH. Cyclopamine inhibited the activation of the Hedgehog signaling pathway. In response to cyclopamine treatment, epithelial and stromal cell proliferation was inhibited; this was concomitant with decreased Ki67, TGF‑β, and b‑FGF expression. On the other hand, epithelial cell apoptosis was enhanced, which was associated with increased Bax and reduced Bcl‑2 expression. Based on these findings, we proposed that cyclopamine may serve as a potential therapeutic agent in the treatment of BPH. Cyclopamine could inhibit epithelial and stromal cell proliferation, and induce epithelial cell apoptosis by suppressing the Hedgehog signaling pathway.
作者机构：
[Shi J.; Yu-Hong W.; Zi-Rong L.] State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[Jian L.; Yuan-Shan H.] The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;[Meng-Yao W.] Qianjin Pharmaceutical Co., Ltd., Zhuzhou, Hunan 412000, China;[Xi Z.] Hunan Provincial Brain Hospital, Changsha, Hunan 410007, China
通讯机构：
[Wang Yu-Hong] S;State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
摘要：
Objective To study the effects of Qianlongtong Capsule (前癃通胶囊) on the histopathology of prostate tissue in rats with benign prostatic hyperplasia (BPH). Methods The BPH model rats was established by orchidoepididymectomy and subcutaneous injection of testosterone propionate. Sixty BPH rats were randomly divided into 5 groups: Control group, model group, Qiantongtong Capsule high-dose group, middle-dose group, low-dose group, with 12 rats in each group. Another 12 rats were recruited as the blank group. The medication was started from the 8th day to the 21st day after modeling, with the dose of 0.51, 1.02 and 2.04g/(kg·d) in the low-dose group, middle-dose group and high-dose group of Qiantongtong Capsule respectively by gavage. Qiantongtong Capsule solution (2.04g/kg·d) was given to the control group by gavage. Equal volume of normal saline (10ml/kg·d) was given to the rats in the model group and the blank group by gavage. The body weight and prostate-related index of the rats were measured, and the pathological changes and ultrastructure of prostate tissue were observed by light microscopy.Results Compared with the blank group, the weight, volume and indexes of prostate were all increased in model group. Meanwhile, the pathology of prostate indicated the hyperplasia of epithelial cell of the gland, the thicken of glandular epithelium, the papillary hyperplastic gland protruded into the glandular cavity, the broaden of glandular cavity, more secretion and the enlargement of the prostate gland epithelium area and stroma area (P<0.05 or P<0.01). Qiantongtong Capsule high-dose group, middle-dose group, low-dose group and control group can effectively improve the pathological changes of prostate in BPH rats, reduce the wet weight, volume and index of prostate, and reduce the area and interstitial area of prostate gland. (P<0.05 or P<0.01). The Qiantongtong Capsule high-dose group had the best effects, which was better than the control group (P<0.05).Conclusion Qianlongtong Capsule can improve the pathological changes of prostate gland epithelium and interstitium of BPH rats, and reduce prostate volume and lower the prostate index.
