AB117. Efficacy and mechanism of combination therapy using Icariin and daily sildenafil citrate for the treatment of erectile dysfunction in a rat model of bilateral cavernous nerves injury

Abstract

The commonly utilized phosphodiesterase type 5 (PDE5) inhibitors does not lead to satisfactory penile erection after radical prostatectomy due to lack of nitric oxide (NO) released from the damaged cavernous nerves (CNs). Of particular interest is that Icariin (ICA) has been demonstrated to increase the expression of neuronal NO synthase (nNOS) in our previous work. In this study, the efficacy and mechanisms ICA in combination with daily sildenafil for the treatment of neurogenic erectile dysfunction (ED) was investigated in a rat model of bilateral CNs injury (BCNI). Sixty male Sprague-Dawley rats injected with 5-ethynyl-2-deoxyuridine (EdU; 50 mg/kg) at newborn were used to track endogenous stem cells (SCs). Fourty-eight rats of BCNI were randomized equally into gavage feeding of vehicle, sildenafil, ICA and sildenafil+ICA, respectively. Twelve sham-operated rats received vehicle treatment and served as control. Interestingly, ICA in combination with sildenafil resulted in better erectile function and effectively preserved the penile size compared with the control and sildenafil groups (P<0.05). In addition, the numbers of nNOS-positive nerves and EdU-positive cells coexpressing Schwann cell marker S100 in the ICA-treated groups were greater compared with the control group (P<0.05). These results indicate that ICA promotes endogenous SCs to differentiate into Schwann cells, which is essential for the regeneration of nNOS-positive nerves after BCNI; on this basis, sildenafil can then improve penile engorgement through the NO-activated smooth muscle relaxation. Therefore, the combined use of ICA and daily sildenafil may be a candidate for the treatment of neurogenic ED in the future.