Shen Baixin, Wang Wei, Ma Long, Wang Shangqian, Ding Liucheng, Chen Zhengsen, Sao Yunpeng, Shen Hua, Wei Zhongqing, Zhang Wei
Department of Urology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Urology. 2014 Oct;84(4):850-6. doi: 10.1016/j.urology.2014.06.015. Epub 2014 Aug 6.
To investigate the role and therapeutic potential of Nuclear factor erythroid-related factor 2 (Nrf2) in oxidative stress induced by di-N-butylphthalate (DBP) in testicular Leydig cells.
Levels of reactive oxygen species (ROS) and Nrf2 in testicles from offspring of mice fed with DBP were studied. Basal ROS and Nrf2 level in mouse TM3 testicular Leydig cells were studied. Cells were treated with silencing or overexpression of Nrf2 in the presence and absence of DBP. Oxidative profiles were examined. Expressions of antioxidant genes downstream of Nrf2 were studied. Therapeutic effect of Nrf2 inducer sulforaphane (SFN) was evaluated.
Leydig cells with low basal Nrf2 and ROS are more vulnerable to DBP. DBP-induced intracellular oxidative stress to a similar extent with Nrf2 knockdown. Nrf2 level was increased together with its target genes, hemeoxygenase 1, quinone 1, and peroxiredoxin 6, after DBP stimulation. Endogenous Nrf2 of Leydig cells was upregulated to battle against ROS. Upregulation of Nrf2 by SFN not only restored the intracellular oxidative toxicity but also cell proliferation and testosterone secretion in response to DBP.
SFN restores oxidative stress induced by DBP in testicular Leydig cells with low basal ROS.
探讨核因子红细胞相关因子2（Nrf2）在邻苯二甲酸二丁酯（DBP）诱导的睾丸间质细胞氧化应激中的作用及治疗潜力。
研究了喂食DBP的小鼠后代睾丸中活性氧（ROS）和Nrf2的水平。研究了小鼠TM3睾丸间质细胞中的基础ROS和Nrf2水平。在有和没有DBP的情况下，用Nrf2沉默或过表达处理细胞。检测氧化谱。研究了Nrf2下游抗氧化基因的表达。评估了Nrf2诱导剂萝卜硫素（SFN）的治疗效果。
基础Nrf2和ROS水平低的间质细胞对DBP更敏感。DBP诱导的细胞内氧化应激程度与Nrf2敲低相似。DBP刺激后，Nrf2水平及其靶基因血红素加氧酶1、醌氧化还原酶1和过氧化物酶体增殖物激活受体6水平升高。间质细胞的内源性Nrf2被上调以对抗ROS。SFN上调Nrf2不仅恢复了细胞内氧化毒性，还恢复了DBP刺激后的细胞增殖和睾酮分泌。
SFN可恢复基础ROS水平低的睾丸间质细胞中DBP诱导的氧化应激。
