Nonhuman primate model of persistent erectile and urinary dysfunction following radical prostatectomy: Feasibility of minimally invasive therapy.
Nonhuman primate model of persistent erectile and urinary dysfunction following radical prostatectomy: Feasibility of minimally invasive therapy.
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DOI：
10.1002/nau.23536
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发表时间：
2018-09
影响因子：
2
通讯作者：
Williams JK
中科院分区：
文献类型：
--
作者：
Zambon JP;Patel M;Hemal A;Badlani G;Andersson KE;Magalhaes RS;Lankford S;Dean A;Williams JK
无论神经保留方法如何，根治性尿道切除术后30-50%的患者会发生持续性尿失禁（UI）和/或勃起功能障碍（艾德）。确定这些患者的潜在治疗方案将需要在发展这些慢性疾病的动物模型中进行测试。目的是描述非人灵长类动物（NHP）模型的持续性尿道切除术后艾德和UI，然后测试尿道周围注射趋化因子CXCL-12的可行性。使用10只成年雄性食蟹猴。两个用于研究正常雄性非人灵长类动物泌尿生殖系统解剖学。5例用于开放性根治性直肠癌切除术（ORP）后3个月和6个月的性行为、峰值体内压（ICP）、腹部漏尿点压（ALPP）测量。另外三只ORP动物在ORP后6周接受超声引导的尿道周围注射趋化因子CXCL 12，并评估UI/艾德长达3个月。这些雄性NHP的前列腺和周围组织的解剖结构、神经支配和血管供应与人类基本相似。ORP导致前列腺沿着神经血管束和精囊腺的完全切除，同时允许膀胱尿道通畅性的稳定恢复。ORP导致ALPP、ICP和性功能持续（6个月）下降。经尿道注射趋化因子CXCL 12是可行的，并对勃起和排尿功能有有益的影响。NHP中的ORP产生持续性勃起和尿路功能障碍。尿道周围注射CXCL-12是可行的，并改善了尿失禁和勃起功能障碍，并表明该模型可用于测试这两种情况的新方法。
Persistent urinary incontinence (UI) and/or erectile dysfunction (ED) occur in 30–50% of post-radical prostatectomy patients regardless of nerve sparing approaches. Identification of potential treatment options for these patients will require testing in an animal model that develops these chronic conditions. The objective was to characterize a nonhuman primate (NHP) model of persistent post-prostatectomy ED and UI and then test the feasibility of periurethral injection of the chemokine CXCL-12. Ten adult male cynomolgus monkeys were used. Two were used for study of normal male nonhuman primate genitourinary anatomy. Five were used for measures of sexual behavior, peak intra-corporal pressure (ICP), abdominal leak point pressures (ALPP) 3 and 6-months post open radical prostatectomy (ORP). Three additional ORP animals received ultrasound-guided peri-urethral injection of chemokine CXCL12 6 weeks after ORP, and UI/ED evaluated for up to 3 months. The anatomy, innervation, and vascular supply to the prostate and surrounding tissues of these male NHPs are substantially similar to those of human beings. ORP resulted in complete removal of the prostate gland along with both neurovascular bundles and seminal vesicles while permitting stable restoration of vesico-urethral patency. ORP produced sustained (6 months) decreases in ALPP, ICP’s, and sexual function. Transurethral injection of chemokine CXCL12 was feasible and had beneficial effects on erectile and urinary function. ORP in NHPs produced persistent erectile and urinary tract dysfunction. Periurethral injection of CXCL-12 was feasible and improved both urinary incontinence and erectile dysfunction and suggests that this model can be used to test new approaches for both conditions.
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