Novel Therapeutic Approach for Neurogenic Erectile Dysfunction: Effect of Neurotrophic Tyrosine Kinase Receptor Type 1 Monoclonal Antibody

作者:Lin, Guiting; Li, Huixi; Zhang, Xiaoyu; Wang, Jianwen; Zaid, Uwais; Sanford, Melissa T.; Tu, Victor; Wu, Alex; Wang, Lin; Tian, Fei; Kotanides, Helen; Krishnan, Venkatesh; Wang, Guifang; Ning, Hongxiu; Banie, Lia; Lin, Ching-Shwun; Deng, Gary G.*; Lue, Tom F.
来源:European Urology, 2015, 67(4): 716-726.
DOI:10.1016/j.eururo.2014.10.013

摘要

Background: Erectile dysED) is a major health issue in aged populations, and neurogenic ED is particularly difficult to treat. Novel therapeutic approaches are needed for treatment of neurogenic ED of peripheral origin. @@@ Objective: To investigate the therapeutic effects of a neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) on erectile function and sexual behavior in a rat model of cavernous nerve injury (CNI). @@@ Design, setting, and participants: In one experiment, 84 male rats were randomly assigned to seven groups. The groups underwent either CNI or sham surgery, subsequent injection into the major pelvic ganglion IMPG) of phosphate-buffered saline (PBS), an immunoglobulin G (IgG) control, or TrkA-mAb, and then intracavernosal (IC) injection of either PBS or varying TrkA-mAb concentrations immediately after surgery and then 1wk later. Erectile function was assessed and histologic/molecular analyses were performed at 6 wk after surgery. In a second experiment, 36 male rats were randomly divided into three groups. The groups underwent CNI or sham surgery and then IC injection of PBS, IgG, or TrkA-mAb immediately after surgery and for 5 wk thereafter. At 6 wk after surgery, the performance of the rats in sexual behavior tests was videotaped. @@@ Intervention: CNI or sham surgery; IMPG of PBS, IgG, or TrkA-mAb; IC injection of PBS or TrkA-mAb. @@@ Outcome measurements and statistical analysis: The intracavernous pressure response to cavernous nerve electrostimulation was measured and midpenile cross-sections were histologically examined. Western blotting (WB) of cavernous tissue protein was performed. Rats were assessed for chasing, mounting, intromission, and ejaculation behaviors during sexual behavior tests. The data were analyzed using one-way analysis of variance followed by the Tukey-Kramer t test.