Vital Paz, Castro Patricia, Ittmann Michael
Department of Pathology and Immunology, Baylor College of Medicine and Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, Texas.
Prostate. 2016 Jan;76(1):58-67. doi: 10.1002/pros.23100. Epub 2015 Sep 29.
Benign prostatic hyperplasia (BPH) is characterized by increased tissue mass in the transition zone of the prostate, which leads to obstruction of urine outflow and significant morbidity in the majority of older men. Plasma markers of oxidative stress are increased in men with BPH but it is unclear whether oxidative stress and/or oxidative DNA damage are causal in the pathogenesis of BPH.
Levels of 8-OH deoxyguanosine (8-OH dG), a marker of oxidative stress, were measured in prostate tissues from normal transition zone and BPH by ELISA. 8-OH dG was also detected in tissues by immunohistochemistry and staining quantitated by image analysis. Nox4 promotes the formation of reactive oxygen species. We therefore created and characterized transgenic mice with prostate specific expression of Nox4 under the control of the prostate specific ARR2PB promoter.
Human BPH tissues contained significantly higher levels of 8-OH dG than control transition zone tissues and the levels of 8-OH dG were correlated with prostate weight. Cells with 8-OH dG staining were predominantly in the epithelium and were present in a patchy distribution. The total fraction of epithelial staining with 8-OH dG was significantly increased in BPH tissues by image analysis. The ARR2PB-Nox4 mice had increased oxidative DNA damage in the prostate, increased prostate weight, increased epithelial proliferation, and histological changes including epithelial proliferation, stromal thickening, and fibrosis when compared to wild type controls.
Oxidative stress and oxidative DNA damage are important in the pathogenesis of BPH.
良性前列腺增生（BPH）的特征是前列腺移行带组织质量增加，这导致大多数老年男性出现尿流梗阻和严重发病情况。BPH男性的氧化应激血浆标志物升高，但尚不清楚氧化应激和/或氧化性DNA损伤在BPH发病机制中是否具有因果关系。
通过酶联免疫吸附测定法（ELISA）测量正常移行带和BPH前列腺组织中氧化应激标志物8-羟基脱氧鸟苷（8-OH dG）的水平。还通过免疫组织化学在组织中检测8-OH dG，并通过图像分析对染色进行定量。Nox4促进活性氧的形成。因此，我们构建并鉴定了在前列腺特异性ARR2PB启动子控制下前列腺特异性表达Nox4的转基因小鼠。
人BPH组织中8-OH dG水平显著高于对照移行带组织，且8-OH dG水平与前列腺重量相关。有8-OH dG染色的细胞主要在上皮中，呈斑片状分布。通过图像分析，BPH组织中8-OH dG上皮染色的总比例显著增加。与野生型对照相比，ARR2PB-Nox4小鼠前列腺中的氧化性DNA损伤增加，前列腺重量增加，上皮增殖增加，并且出现包括上皮增殖、基质增厚和纤维化在内的组织学变化。
氧化应激和氧化性DNA损伤在BPH发病机制中起重要作用。
