Department of Cell Biology, Institute of Biology, UNICAMP-University of Campinas, Campinas, Sao Paulo, Brazil.
Microsc Res Tech. 2010 Oct;73(11):1036-44. doi: 10.1002/jemt.20828.
Doxazosin (DOX), an α-adrenoceptor antagonist, induces the relaxation of smooth muscle cell tonus and reduces the clinical symptoms of benign prostatic hyperplasia (BPH). However, the effects of DOX in the prostate stromal microenvironment are not fully known. In a previous study, we showed that DOX treatment for 30 days increased deposition of collagen fibers in the three rat prostatic lobes. Herein, we investigated the effects of DOX on stromal cell ultrastructure and elastic fiber deposition. Adult Wistar rats were treated with DOX (25 mg/kg/day); and the ventral, dorsal, and anterior prostates were excised at 30 days of treatment. The prostatic lobes were submitted to histochemical and stereological-morphometric analyze and transmission electron microscopy (TEM). Histochemical staining plus stereological analysis of the elastic fiber system showed that DOX-treated prostatic lobes presented more elaunin and elastic fibers than controls, mainly in the ventral lobe. Ultrastructural analysis showed that fibroblasts and smooth muscle cells from DOX-treated prostates presented active synthetic phenotypes, evidenced by enlarged rough endoplasmic reticulum and Golgi apparatus cisterns, and confirmed the observation of thickened elaunin fibers. Our findings suggest that, under α-adrenergic blockade by DOX, the fibroblasts become more active and smooth muscle cells shift from a predominantly contractile to a more synthetic phenotype. The deposition of collagen and elastic system fibers in the prostatic stroma may counterbalance the absence of smooth muscle tone during α-blockers treatment.
多沙唑嗪（DOX），一种α-肾上腺素能受体拮抗剂，可引起平滑肌细胞紧张度松弛，并减轻良性前列腺增生（BPH）的临床症状。然而，DOX 在前列腺基质微环境中的作用尚不完全清楚。在之前的研究中，我们发现 DOX 治疗 30 天可增加三个大鼠前列腺叶中胶原纤维的沉积。在此，我们研究了 DOX 对基质细胞超微结构和弹性纤维沉积的影响。成年 Wistar 大鼠用 DOX（25mg/kg/天）处理；在治疗 30 天后切除腹侧、背侧和前侧前列腺。对前列腺叶进行组织化学和体视学形态计量分析和透射电子显微镜（TEM）检查。弹性纤维系统的组织化学染色加体视学分析显示，DOX 处理的前列腺叶比对照组有更多的弹性蛋白纤维和弹性纤维，主要在腹侧叶。超微结构分析显示，来自 DOX 处理的前列腺的成纤维细胞和平滑肌细胞呈现出活跃的合成表型，这表现为粗面内质网和高尔基器池扩张，证实了增厚的弹性蛋白纤维的观察结果。我们的发现表明，在 DOX 阻断α-肾上腺素能作用下，成纤维细胞变得更加活跃，平滑肌细胞从主要收缩型向更合成型转变。前列腺基质中胶原和弹性系统纤维的沉积可能抵消了α-阻滞剂治疗期间平滑肌张力的缺失。
