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通过口服异黄酮建立大鼠前列腺炎模型及其特征

Development of rat prostatitis model by oral administration of isoflavone and its characteristics.

作者信息

Kwon S M, Kim S I, Chun D C, Cho N H, Chung B C, Park B W, Hong S J

机构信息

Department of Urology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul 120-752, Korea.

出版信息

Yonsei Med J. 2001 Aug;42(4):395-404. doi: 10.3349/ymj.2001.42.4.395.

DOI:10.3349/ymj.2001.42.4.395
PMID:11519081
Abstract

Inflammation of the prostate can be induced experimentally in rats by the subcutaneous administration of estrogen. However, it is usually achieved at the price of some alteration in the sex steroid hormone balance and morphological changes in the prostate. In this study, a soy-extracted isoflavone mixture with weak estrogenic activity was administered orally in an attempt to induce prostatitis in a more physiologic way and to characterize the inflammation induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2 groups. The control group was fed with only an AIN-76A diet containing no detectable phytoestrogen and the experimental group was fed with AIN-76A and a soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300 mg/kg body weight for 9 weeks. The sequential body weight and prostate weight at necropsy were measured. A histologic examination and histomorphometry assessed the changes in the prostate. The serum concentrations of testosterone and dihydrotestosterone were measured to estimate the effects on the androgen level. Intraprostatic concentrations of genistein and daidzein were measured by gas chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation was apparent in the control group, severe inflammatory changes in the stroma, increased epithelial detachment and inflammatory exudates within the glandular lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the experimental group. However, there was no significant difference in the ventral prostate between the two groups. The daidzein and genistein concentrations in both the lateral and ventral prostates were significantly higher in the experimental group than in the control group where no isoflavone was detectable. In addition, the concentrations were much higher in the dorsolateral than in the ventral prostate. Although the body weight gain was not consistent in the experimental group, there were no significant differences in the prostate weight and serum androgen level between groups. In summary, when a soy-extracted genistein and daidzein-rich isoflavone mixture was administered orally into rats, prostatic inflammation with characteristic lobe specificity developed. The present method of inducing prostatitis seems to be a more physiologic than an estrogen-induced experimental model, and sequential pharmacokinetic studies might help in establishing this model as a more valuable tool in assisting future research in this field.

摘要

通过皮下注射雌激素可在大鼠中实验性诱导前列腺炎症。然而,通常是以性类固醇激素平衡的某些改变以及前列腺的形态变化为代价来实现的。在本研究中,口服给予具有弱雌激素活性的大豆提取物异黄酮混合物,试图以更生理的方式诱导前列腺炎并对所诱导的炎症进行特征描述。总共36只8周龄的雄性斯普拉格 - 道利大鼠被分为2组。对照组仅喂食不含可检测到的植物雌激素的AIN - 76A饮食,实验组喂食AIN - 76A和大豆提取物异黄酮混合物(染料木黄酮60.0%和黄豆苷元19.6%),剂量为300 mg/kg体重,持续9周。在尸检时测量连续的体重和前列腺重量。组织学检查和组织形态计量学评估前列腺的变化。测量血清睾酮和二氢睾酮浓度以评估对雄激素水平的影响。通过气相色谱/质谱法(GC/MS)测量前列腺内染料木黄酮和黄豆苷元的浓度。虽然对照组未出现前列腺炎症的迹象,但在实验组超过80%(15/18)的大鼠中观察到背外侧前列腺基质中的严重炎症变化、上皮脱落增加以及腺腔内的炎性渗出物。然而,两组之间腹侧前列腺没有显著差异。实验组外侧和腹侧前列腺中的黄豆苷元和染料木黄酮浓度均显著高于未检测到异黄酮的对照组。此外,背外侧前列腺中的浓度远高于腹侧前列腺。尽管实验组的体重增加不一致,但两组之间前列腺重量和血清雄激素水平没有显著差异。总之,当将富含染料木黄酮和黄豆苷元的大豆提取物异黄酮混合物口服给予大鼠时,会出现具有特征性叶特异性的前列腺炎症。目前诱导前列腺炎的方法似乎比雌激素诱导的实验模型更具生理性,并且连续的药代动力学研究可能有助于将该模型确立为该领域未来研究中更有价值的工具。

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