Department of Biology, UNESP - Univ Estadual Paulista, IBILCE - Institute of Biosciences, Humanities, São José do Rio Preto, SP, Brazil.
Micron. 2012 Feb;43(2-3):326-33. doi: 10.1016/j.micron.2011.09.009. Epub 2011 Sep 29.
The stromal microenvironment is pivotal to prostate physiology and malign transformation. Diabetes leads to testosterone withdrawal and affects the prostate stromal compartment and smooth muscle cells in a similar way to that observed after castration. However the response of these cells and their involvement in extracellular matrix remodeling is not satisfactorily understood. We investigated the changes caused in the short term (one week) by alloxan-induced diabetes in the stromal components of the rat ventral prostate (VP) with an emphasis on morphological alterations of stromal cells, their conversion to a myofibroblast phenotype and the remodeling of extracellular matrix and the influence of insulin therapy. Adult male Wistar rats were assigned into untreated diabetic (n=12), insulin-treated (n=8) diabetic and control (n=10) groups. Diabetes was induced by means of the injection of alloxan (40 mg/kg b.w.), while the control animals received saline solution only. Insulin (5 UI) was administered daily for one week after diabetes diagnosis. Testosterone and estrogen plasma levels were determined. VP was analyzed using transmission electron microscopy. The main stromal cells were identified by means of light microscopy, using immunocytochemistry for specific markers - vimentin for fibroblasts, α-actin for smooth muscle cells (smc) and vimentin/calponin for myofibroblasts, following the estimation of their relative frequency and absolute volume by means of stereology. After one week diabetes led to a marked decrease in testosterone levels and an atrophy of about 35% in the VP. The relative frequency of smc and collagen fibers increased in the VP of diabetic rats but their absolute weight remained unchanged. Experimental diabetes promptly altered smc morphology which assumed at the ultrastructural level a shrunken appearance with the approximation of cytoplasmic dense bodies and also exhibited a decreased immunoreactivity to calponin. The conversion of stromal cells to a myofibroblast phenotype did not occur in alloxan-induced diabetes, as evaluated by double immunoreaction to calponin and vimentin. Insulin treatment maintained testosterone levels and preserved at least partly the cell morphology and collagen fiber organization of the prostate stroma in short-term diabetes. The apparent collagen increase observed by means of microscopic analysis in the stromal prostate compartment in the short term after diabetes is mainly associated with gland atrophy and does not involve the formation of new collagen fibers, the generation of myofibroblast-like cells or the acquisition of a secretory phenotype by stromal cells.
基质微环境对前列腺生理学和恶性转化至关重要。糖尿病导致睾酮耗竭，并以类似于去势后观察到的方式影响前列腺基质区室和平滑肌细胞。然而，这些细胞的反应及其在细胞外基质重塑中的作用尚不完全清楚。我们研究了短期（一周）用链脲佐菌素诱导糖尿病对大鼠腹侧前列腺（VP）基质成分的影响，重点研究了基质细胞的形态改变、向肌成纤维细胞表型的转化以及细胞外基质的重塑，以及胰岛素治疗的影响。成年雄性 Wistar 大鼠被分为未治疗的糖尿病（n=12）、胰岛素治疗的糖尿病（n=8）和对照组（n=10）。糖尿病通过注射链脲佐菌素（40mg/kg b.w.）诱导，而对照组仅接受生理盐水。糖尿病诊断后，每天给予胰岛素（5UI）治疗一周。测定睾酮和雌激素的血浆水平。使用透射电子显微镜分析 VP。通过使用特定标记物的免疫细胞化学 - 纤维母细胞的波形蛋白、平滑肌细胞（smc）的α-肌动蛋白和肌成纤维细胞的波形蛋白/钙调蛋白 - 对主要基质细胞进行光镜鉴定，通过体视学估计其相对频率和绝对体积。一周后，糖尿病导致睾酮水平明显下降，VP 萎缩约 35%。糖尿病大鼠 VP 中 smc 和胶原纤维的相对频率增加，但绝对重量保持不变。实验性糖尿病迅速改变了 smc 的形态，在超微结构水平上表现为细胞质致密体的接近和收缩，也表现出对钙调蛋白的免疫反应性降低。在链脲佐菌素诱导的糖尿病中，基质细胞向肌成纤维细胞表型的转化并未发生，如钙调蛋白和波形蛋白的双重免疫反应所示。胰岛素治疗维持了睾酮水平，并在短期糖尿病中至少部分保留了前列腺基质的细胞形态和胶原纤维组织。通过显微镜分析观察到的短期糖尿病后前列腺基质区室中明显的胶原增加主要与腺体萎缩有关，不涉及新胶原纤维的形成、肌成纤维细胞样细胞的生成或基质细胞获得分泌表型。
