Department of Biology, Institute of Biosciences, Letters and Exact Sciences, São Paulo State University-Unesp, São José do Rio Preto, São Paulo, Brazil.
Int J Exp Pathol. 2010 Apr;91(2):144-54. doi: 10.1111/j.1365-2613.2009.00696.x. Epub 2009 Dec 22.
The effects of experimental type 1 diabetes were investigated in the acinar epithelium of rat ventral prostate, focusing on the rates of cell proliferation and the frequency of apoptosis and p63-positive cells. Type 1 diabetes was induced in adult male Wistar rats by a single alloxan administration (42 mg/kg b.w.) and its effects were analysed for 1 week and 3 months after the establishment of the disease. A group of diabetic rats was treated daily with 5 IU of insulin during 1 week after diabetes had been diagnosed. Immunocytochemical methods for the localization of cell proliferation antigen (PCNA), androgen receptor (AR) and p63 protein were carried out, and apoptotic cells were identified by TUNEL essay. In diabetic rats, testosterone levels reduced drastically after 1 week and in a lower degree after 3 months. In short-term diabetic rats, cell proliferation decreased, and in medium-term, epithelial apoptotic rates increased. In both periods after the onset of diabetes, the frequency of p63-positive cells doubled. Insulin treatment was effective in preventing testosterone decrease, p63-positive cell increase and apoptotic rates, but did not interfere in cell proliferation. This investigation shows that, soon after diabetes onset, there are important modifications in cell proliferation within the acinar prostatic epithelium, and in longer term, there is a marked impact on kinetics of differentiation and cell death, which may initially be attributable to an androgenic fall, but is probably also because of other factors related to diabetes, as changes are considerably different from those resulting from castration.
本研究聚焦于成年雄性 Wistar 大鼠胰岛上皮细胞的增殖率、凋亡率和 p63 阳性细胞频率,以研究实验性 1 型糖尿病的影响。通过单次腹腔注射(42mg/kg b.w.)链脲佐菌素诱导大鼠产生 1 型糖尿病,分别于糖尿病建立后 1 周和 3 个月分析其影响。在诊断为糖尿病后的 1 周内,每天给部分糖尿病大鼠注射 5IU 的胰岛素。采用免疫细胞化学方法定位细胞增殖抗原(PCNA)、雄激素受体(AR)和 p63 蛋白,并用 TUNEL 法鉴定凋亡细胞。1 周后,糖尿病大鼠的睾酮水平急剧下降,3 个月后则下降较少。短期糖尿病大鼠的细胞增殖减少,中期上皮细胞的凋亡率增加。在糖尿病发病后的这两个时期,p63 阳性细胞的频率都增加了一倍。胰岛素治疗能有效预防睾酮下降、p63 阳性细胞增加和凋亡率增加,但对细胞增殖没有影响。本研究表明,在糖尿病发病后不久,腺泡前列腺上皮细胞的增殖就会发生重要变化,在更长的时间内,分化和细胞死亡的动力学也会受到明显影响,这可能最初归因于雄激素下降,但也可能是由于与糖尿病相关的其他因素所致,因为这些变化与去势引起的变化有很大的不同。