Department of Clinical Sciences, and Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina; Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado.
Department of Environmental and Radiologic Health Sciences, Colorado State University, Fort Collins, Colorado.
Int J Radiat Oncol Biol Phys. 2015 Mar 15;91(4):796-806. doi: 10.1016/j.ijrobp.2014.12.025.
PURPOSE/OBJECTIVES: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation.
Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes.
SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT.
This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is warranted.
目的/目标：前列腺癌放射治疗后常发生勃起功能障碍；然而，放射诱导勃起功能障碍（RI-ED）的发病机制仍知之甚少。本研究建立了一种新的动物模型，采用立体定向体部放射治疗（SBRT）照射狗的前列腺、神经血管束（NVB）和阴茎球（PB），研究仅照射 NVB 或 PB 以及同时照射前列腺、NVB 和 PB 三种组织时不同剂量放射后的血管和神经损伤。
通过 5 次分割 SBRT，分别对前列腺、NVB 和 PB 给予 50、40 或 30Gy 照射，或对 NVB 或 PB 给予 50Gy 照射。在 SBRT 前后进行阴部神经和球海绵体肌的电生理研究以及盆腔灌注的超声研究。这些生物测定的结果与组织病理学变化相关联。
SBRT 导致收缩期上升时间减慢，提示动脉通畅性下降。观察到内阴部动脉对血管活性药物反应的改变，其中 40 和 50Gy 时 SBRT 导致罂粟碱的收缩期上升时间减慢；这些变化似乎具有一定的剂量依赖性。高剂量时阴茎神经的神经丝含量降低，当 PB 照射时比 NVB 照射时更明显。这些发现与 SBRT 后阴部神经运动神经传导速度减慢一致。
这是首次报道前列腺照射可引起形态学动脉损伤，同时伴有内阴部动脉张力改变，并且阴部神经运动功能下降归因于轴突变性和丢失。进一步研究这些结构损伤在 RI-ED 中的作用是必要的。
