PDF(Pubmed)
Abstract：
OBJECTIVE: Neurogenic erectile dysfunction (ED) is a common side effect of radical prostatectomy (RP) because of cavernous nerve damage. In these patients, the production of nitric oxide (NO), which is important for erection, is decreased in the corpus cavernosum. Therefore, NO donors are useful for post-RP ED. However, short half-life and systemic side effects are problems of NO application in ED therapy. To avert these problems, we developed a red-light controllable NO releaser, NORD-1. This study aimed to investigate the effect of NORD-1 and red-light irradiation on neurogenic ED using a rat model of bilateral cavernous nerve injury (BCNI).
METHODS: BCNI and sham operations were conducted on 8-week-old rats. After 4 weeks, erectile function was evaluated using changes in intracavernous pressure (ICP) during electrostimulation of the cavernous nerve. ICP was measured under three conditions; without NORD-1 and red-light irradiation, with NORD-1 and without red-light irradiation, and with NORD-1 and red-light irradiation. SiR650 which absorbs red-light but does not release NO was used for the negative control. After the experiment, localization of NORD-1 was observed using a microscope.
RESULTS: Erectile function in a BCNI rat model was significantly decreased compared to sham-operated rats (p<0.05). After injecting NORD-1 into the penis, erectile function did not change without red-light irradiation. However, the combination of NORD-1 and red-light irradiation significantly improved erectile function (p<0.05) without affecting systemic arterial pressure. In contrast, when SiR650 was used, erectile function did not change in all three conditions. NORD-1 was detected only in the corpus cavernosum and not in the urethra and dorsal vein.
CONCLUSIONS: NORD-1 combined with red-light irradiation is effective for ED induced by cavernous nerve injury. This treatment may have low risks of hypotension and urinary incontinence, and it can replace the current treatment for post-RP ED.
METHODS: BCNI and sham operations were conducted on 8-week-old rats. After 4 weeks, erectile function was evaluated using changes in intracavernous pressure (ICP) during electrostimulation of the cavernous nerve. ICP was measured under three conditions; without NORD-1 and red-light irradiation, with NORD-1 and without red-light irradiation, and with NORD-1 and red-light irradiation. SiR650 which absorbs red-light but does not release NO was used for the negative control. After the experiment, localization of NORD-1 was observed using a microscope.
RESULTS: Erectile function in a BCNI rat model was significantly decreased compared to sham-operated rats (p<0.05). After injecting NORD-1 into the penis, erectile function did not change without red-light irradiation. However, the combination of NORD-1 and red-light irradiation significantly improved erectile function (p<0.05) without affecting systemic arterial pressure. In contrast, when SiR650 was used, erectile function did not change in all three conditions. NORD-1 was detected only in the corpus cavernosum and not in the urethra and dorsal vein.
CONCLUSIONS: NORD-1 combined with red-light irradiation is effective for ED induced by cavernous nerve injury. This treatment may have low risks of hypotension and urinary incontinence, and it can replace the current treatment for post-RP ED.
摘要：
目的：由于海绵状神经损伤，神经源性勃起功能障碍（ED）是前列腺癌根治术（RP）的常见副作用。在这些患者中,一氧化氮（NO）的产生，这对勃起很重要，海绵体减少。因此,NO供体对于RP后ED是有用的。然而,半衰期短和全身副作用是NO在ED治疗中应用的问题。为了避免这些问题，我们开发了一种红光可控的NO释放器，NORD-1.本研究旨在利用双侧海绵状神经损伤（BCNI）大鼠模型研究NORD-1和红光照射对神经源性ED的影响。
方法：对8周龄大鼠进行BCNI和假手术。4周后,使用电刺激海绵体神经期间海绵体内压（ICP）的变化来评估勃起功能。在三种条件下测量ICP；没有NORD-1和红光照射，有NORD-1并且没有红光照射，用NORD-1和红光照射。将吸收红光但不释放NO的SiR650用于阴性对照。实验之后,使用显微镜观察NORD-1的定位。
结果：与假手术大鼠相比，BCNI大鼠模型的勃起功能明显降低（p<0.05）。将NORD-1注入阴茎后,没有红光照射，勃起功能没有改变。然而,NORD-1和红光照射的组合显着改善了勃起功能（p<0.05），而不影响全身动脉压。相比之下,当使用SiR650时，在所有三种情况下，勃起功能均未发生变化。仅在海绵体中检测到NORD-1，而在尿道和背静脉中未检测到。
结论：NORD-1联合红光照射治疗海绵状神经损伤所致ED有效。这种治疗可能具有低血压和尿失禁的低风险，它可以代替RP后ED的当前治疗。
方法：对8周龄大鼠进行BCNI和假手术。4周后,使用电刺激海绵体神经期间海绵体内压（ICP）的变化来评估勃起功能。在三种条件下测量ICP；没有NORD-1和红光照射，有NORD-1并且没有红光照射，用NORD-1和红光照射。将吸收红光但不释放NO的SiR650用于阴性对照。实验之后,使用显微镜观察NORD-1的定位。
结果：与假手术大鼠相比，BCNI大鼠模型的勃起功能明显降低（p<0.05）。将NORD-1注入阴茎后,没有红光照射，勃起功能没有改变。然而,NORD-1和红光照射的组合显着改善了勃起功能（p<0.05），而不影响全身动脉压。相比之下,当使用SiR650时，在所有三种情况下，勃起功能均未发生变化。仅在海绵体中检测到NORD-1，而在尿道和背静脉中未检测到。
结论：NORD-1联合红光照射治疗海绵状神经损伤所致ED有效。这种治疗可能具有低血压和尿失禁的低风险，它可以代替RP后ED的当前治疗。
