Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland.
Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland.
Int J Radiat Oncol Biol Phys. 2017 Nov 1;99(3):680-688. doi: 10.1016/j.ijrobp.2017.06.2449. Epub 2017 Jun 27.
PURPOSE/OBJECTIVES: Radiation-induced erectile-dysfunction (RiED) is one of the most common side effects of radiation therapy (RT) and significantly reduces the quality of life (QoL) of cancer patients. Approximately 50% of prostate cancer patients experience RiED within 3 to 5 years after completion of RT. A series of vascular, muscular, and neurogenic injuries after prostate RT lead to RiED; however, the precise role of RT-induced neurogenic injury in RiED has not been fully established. The cavernous nerves (CN) are postganglionic parasympathetic nerves located beside the prostate gland that assist in penile erection. This study was designed to investigate the role of CN injury, tissue damage, and altered signaling pathways in an RiED rat model.
Male rats were exposed to a single dose of 25 Gy prostate-confined RT. Erectile function was evaluated by intracavernous pressure (ICP) measurements conducted both 9 and 14 weeks after RT. Neuronal injury was evaluated in the CN using quantitative polymerase chain reaction, conduction studies, transmission electron microscopy, and immunoblotting. Masson trichrome staining was performed to elucidate fibrosis level in penile tissues.
There were significant alterations in the ICP (P<.0001) of RT rats versus non-RT rats. TEM analysis showed decreased myelination, increased microvascular damage, and progressive axonal atrophy of the CN fibers after RT. Electrophysiologic analysis showed significant impairment of the CN conduction velocity after RT. RT also significantly increased RhoA/Rho-associated protein kinase 1 (ROCK1) mRNA and protein expression. In addition, penile tissue showed increased apoptosis and fibrosis 14 weeks after RT.
RT-induced CN injury may contribute to RiED; this is therefore a rationale for developing novel therapeutic strategies to mitigate CN and tissue damage. Moreover, further investigation of the RhoA/ROCK pathway's role in mitigating RiED is necessary.
目的/目标：放射性勃起功能障碍（RiED）是放射治疗（RT）最常见的副作用之一，显著降低了癌症患者的生活质量（QoL）。大约 50%的前列腺癌患者在 RT 完成后 3 至 5 年内会出现 RiED。前列腺 RT 后一系列血管、肌肉和神经损伤导致 RiED；然而，RT 诱导的神经损伤在 RiED 中的确切作用尚未完全确定。海绵体神经（CN）是位于前列腺旁的节后副交感神经，有助于阴茎勃起。本研究旨在探讨 CN 损伤、组织损伤和信号通路改变在 RiED 大鼠模型中的作用。
雄性大鼠接受单次 25Gy 前列腺限制 RT。RT 后 9 和 14 周通过海绵体内压（ICP）测量评估勃起功能。使用定量聚合酶链反应、传导研究、透射电子显微镜和免疫印迹评估 CN 中的神经元损伤。Masson 三色染色法阐明阴茎组织中的纤维化水平。
与非 RT 大鼠相比，RT 大鼠的 ICP 有明显改变（P<.0001）。TEM 分析显示，RT 后 CN 纤维的髓鞘减少、微血管损伤增加和轴突进行性萎缩。电生理分析显示，RT 后 CN 传导速度显著受损。RT 还显著增加了 RhoA/Rho 相关蛋白激酶 1（ROCK1）mRNA 和蛋白表达。此外，RT 后 14 周阴茎组织显示出增加的细胞凋亡和纤维化。
RT 诱导的 CN 损伤可能导致 RiED；因此，开发减轻 CN 和组织损伤的新治疗策略是合理的。此外，有必要进一步研究 RhoA/ROCK 通路在减轻 RiED 中的作用。
