Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA 94143-0738, USA.
Eur Urol. 2011 Feb;59(2):286-96. doi: 10.1016/j.eururo.2010.10.034. Epub 2010 Oct 26.
Cavernous nerve (CN) injury during radical prostatectomy (RP) causes CN degeneration and secondary penile fibrosis and smooth muscle cell (SMC) apoptosis. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that further inhibits multiple cytokine pathways involved in nerve degeneration, apoptosis, and fibrosis.
To evaluate whether PTX enhances erectile function in a rat model of CN injury. DESIGN, SETTING AND INTERVENTIONS: Forty male Sprague-Dawley rats underwent CN crush injury and were randomized to oral gavage feeding of phosphate-buffered saline (vehicle) or PTX 25, PTX 50, or PTX 100 mg/kg per day. Ten animals underwent sham surgery and received vehicle treatment. Treatment continued for 28 d, followed by a wash-out period of 72 h. An additional eight rats underwent resection of the major pelvic ganglion (MPG) for tissue culture and examination of direct effects of PTX on neurite sprouting.
Intracavernous pressure recording on CN electrostimulation, immunohistologic examination of the penis and the CN distal to the injury site, and length of neurite sprouts in MPG culture.
Daily oral gavage feeding of PTX resulted in significant improvement of erectile function compared to vehicle treatment in all treated groups. After treatment with PTX 50 and PTX 100 mg/kg per day, the expression of neuronal nitric oxide synthase in the dorsal penile nerve was significantly higher than in vehicle-treated rats. Furthermore, PTX treatment prevented collagen deposition and SMC loss in the corpus cavernosum. In the CN, signs of Wallerian degeneration were ameliorated by PTX treatment. MPG culture in medium containing PTX resulted in a significant increase of neurite length.
PTX treatment following CN injury in rats improved erectile recovery, enhanced nerve regeneration, and preserved the corpus cavernosum microarchitecture. The clinical availability of this compound merits application in penile rehabilitation studies following RP in the near future.
根治性前列腺切除术（RP）过程中导致的海绵体神经（CN）损伤会引起 CN 变性以及继发性阴茎纤维化和平滑肌细胞（SMC）凋亡。己酮可可碱（PTX）是一种磷酸二酯酶抑制剂，可进一步抑制多个涉及神经变性、凋亡和纤维化的细胞因子途径。
评估己酮可可碱是否能增强 CN 损伤大鼠模型的勃起功能。
设计、地点和干预措施：40 只雄性 Sprague-Dawley 大鼠行 CN 挤压伤，并随机接受磷酸缓冲盐水（载体）或 25、50 或 100 mg/kg/天的 PTX 口服灌胃。10 只动物行假手术并接受载体治疗。治疗持续 28 天，随后洗脱 72 小时。另外 8 只大鼠行阴部神经节（MPG）切除术，用于组织培养和直接检测 PTX 对神经突发芽的影响。
CN 电刺激下的海绵体内压记录、阴茎和损伤部位远端 CN 的免疫组织化学检查，以及 MPG 培养中神经突的长度。
与载体治疗相比，所有治疗组的大鼠经口灌胃给予 PTX 后，勃起功能均显著改善。与载体治疗组相比，PTX 50 和 100 mg/kg/天治疗组阴茎背神经中的神经元型一氧化氮合酶表达明显更高。此外，PTX 治疗可防止阴茎海绵体中的胶原沉积和 SMC 丢失。在 CN 中，PTX 治疗可改善 Wallerian 变性的迹象。含 PTX 的培养基中培养 MPG 会导致神经突长度显著增加。
在大鼠 CN 损伤后给予 PTX 治疗可改善勃起功能恢复，增强神经再生，并保持阴茎海绵体的微观结构。该化合物的临床可用性使得其有望在不久的将来应用于 RP 后阴茎康复研究。
