Ito Hideaki, Wang Dong, Zha Xinmin, Inamura So, Seki Masaya, Taga Minekatsu, Yokoyama Osamu
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan.
Life Sci. 2018 Jan 15;193:252-256. doi: 10.1016/j.lfs.2017.10.037. Epub 2017 Nov 8.
Androgen deprivation therapy has been widely used for the treatment of prostate cancer. While sexual side effects including decreased sexual desire and function are well studied, there are only limited reports about its influences on lower urinary tract symptoms. The aim of this study is to clarify the influences of castration in male rats.
Ten-week-old male rats were divided into treatment group (bilateral orchiectomy) and control group (sham surgery). Two-months after the surgery, adenosine triphosphate (ATP), prostaglandin E2 (PGE2), and nerve growth factor (NGF) released from stretched bladder epithelium were measured by luciferin-luciferase assay or ELISA. The mRNA levels of bladder cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were determined by real-time PCR. The protein level of bladder COX-2 was analyzed by western blot analysis. Bio-Plex Pro cytokine assay was performed to quantify the level of proinflammatory cytokine interleukin (IL)-1β in the bladder.
The PGE release from stretched bladder epithelium was significantly increased after castration, which increased more than 50% compared with control. On the other hand, those of ATP and NGF were not different from those of the controls. Testosterone replacement restored the PGE increase. Castration significantly increased bladder IL-1β protein level and COX-2 at both mRNA and protein levels, whereas caused no marked changes in the COX-1 mRNA level.
These findings suggest that castration induces inflammation in the rat bladder, which causes elevated PGE release from bladder epithelium and may finally contribute to the disruption of bladder storage function.
雄激素剥夺疗法已广泛用于前列腺癌的治疗。虽然包括性欲和性功能下降在内的性副作用已得到充分研究，但关于其对下尿路症状影响的报道却很有限。本研究的目的是阐明去势对雄性大鼠的影响。
将10周龄雄性大鼠分为治疗组（双侧睾丸切除术）和对照组（假手术）。手术后两个月，通过荧光素-荧光素酶测定法或酶联免疫吸附测定法测量拉伸膀胱上皮释放的三磷酸腺苷（ATP）、前列腺素E2（PGE2）和神经生长因子（NGF）。通过实时聚合酶链反应测定膀胱环氧化酶-1（COX-1）和环氧化酶-2（COX-2）的mRNA水平。通过蛋白质免疫印迹分析膀胱COX-2的蛋白质水平。采用生物芯片多功能细胞因子检测法对膀胱中促炎细胞因子白细胞介素（IL）-1β水平进行定量分析。
去势后拉伸膀胱上皮释放的PGE显著增加，与对照组相比增加了50%以上。另一方面，ATP和NGF的释放与对照组无差异。睾酮替代可恢复PGE的升高。去势显著增加膀胱IL-1β蛋白水平以及COX-2的mRNA和蛋白水平，而对COX-1 mRNA水平无明显影响。
这些发现表明，去势可诱导大鼠膀胱炎症，导致膀胱上皮PGE释放增加，最终可能导致膀胱储存功能受损。
