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Senile changes of human prostate-developmental mechanisms of benign prostatic hyperplasia and senile changes in smooth muscle cells in the prostate

人前列腺的老年性变化——良性前列腺增生的发育机制及前列腺平滑肌细胞的老年性变化

基本信息

批准号：
08457427
负责人：
TSUKAMOTO Taiji
金额：
$ 4.42万
依托单位：
Sapporo Medical University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

Development of benign prostatic hyperplasia (BPH) partly depend on ageing. We investigated the several issues of 1) morphological changes of human prostate with ageing, 2) functional changes with ageing of smooth muscle cells of the prostate, 3)regulations of epithelial and mesenchymal cells of the prostate by androgen and growth factors. These studies brought us the following results.1) Community-based study for urinary symptoms suggests that development of BPH may involve at least 2 major processes, that is the transition from normal to diffusely enlarged hyperplasia at approximately 50 years of age and subsequent growth through nodular enlarged hyperplasia.2) We established from guinea-pig the cell line of smooth muscles cells, which was confirmed by morphological and functional studies. This cell line may be utilised asan in vitro experimental model.3) Contractile function of smooth muscle of the prostate in aged guinea-pig was reduced, when compared with those of young, suggesting that ageing may affect function of smooth muscle cells.4) Reduced function of bladder smooth muscle was involved in causes of poor voiders with lower urinary tract obstruction by BPH.Agents to make function of bladder smooth muscle improve may be necessary for relief of poor condition of voiding.5) Loss of balance between cell proliferation and apoptosis in the prostate may be involved in development of BPH.Decrease of androgen enhances mRNA expression of transforming growth factor (TGF)-beta in mesenchymal cells in the prostate, resulting in not only loss of epithelial cells by apoptosis but enhanced proliferation of mesenchymal cells mediated by fibroblast growth factor. The latter evidence may be responsible for development of BPH.

良性前列腺增生（BPH）的发生与年龄有关。我们研究了几个问题：1）人前列腺的形态学变化与老化，2）功能的变化与老化的平滑肌细胞的前列腺，3）调节上皮细胞和间充质细胞的前列腺由雄激素和生长因子。这些研究给我们带来了以下结果：1）以社区为基础的泌尿系统症状研究表明，BPH的发展可能涉及至少两个主要过程，即在大约50岁时从正常到弥漫性扩大增生的转变，以及随后通过结节性扩大增生的生长。形态学和功能学研究证实了这一点。3）老年豚鼠前列腺平滑肌收缩功能较青年豚鼠降低，这表明衰老可能会影响平滑肌细胞的功能。4）膀胱平滑肌功能降低是BPH所致下尿路梗阻排尿困难的原因之一。改善膀胱平滑肌功能的药物5）前列腺细胞增殖与凋亡失衡可能参与了BPH的发生发展，雄激素减少可增强前列腺间充质细胞转化生长因子（TGF）-β mRNA的表达，不仅导致上皮细胞凋亡减少，还可增强成纤维细胞生长因子介导的间充质细胞增殖。后一种证据可能是导致BPH发展的原因。