ABSTRACT
Postprostatectomy erectile dysfunction (pPED) remains a current problem despite improvements in surgical techniques. Vacuum therapy is clinically confirmed as a type of pPED rehabilitation. However, its underlying mechanisms are incompletely understood. Recently, autophagy and apoptosis were extensively studied in erectile dysfunction resulting from diabetes, senescence, and androgen deprivation but not in the context of pPED and vacuum therapy. Therefore, this study was designed to investigate the roles of autophagy and apoptosis in pPED and vacuum therapy. Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: the control group, bilateral cavernous nerve crush (BCNC) group, and BCNC + vacuum group. After 4 weeks of treatment, intracavernosal pressure was used to evaluate erectile function. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to measure the molecular expression. TdT-mediated dUTP nick-end labeling staining was used to assess apoptosis. Transmission electron microscopy was used to observe autophagosomes. After treatment, compared with those of the BCNC group, erectile function and cavernosal hypoxia had statistically significantly improved (P < 0.05). Apoptosis and the relative protein expression of B-cell lymphoma-2-associated X and cleaved Caspase3 were decreased (P < 0.05). Autophagy-related molecules such as phosphorylated unc-51-like autophagy-activating kinase 1 (Ser757) and p62 were decreased. Beclin1, microtubule-associated protein 1 light chain 3 A/B, and autophagosomes were increased (P < 0.05). Besides, the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway, as a negative regulator of autophagy to some degree, was inhibited. This study revealed that vacuum therapy ameliorated pPED in BCNC rats by inhibiting apoptosis and activating autophagy.
ABSTRACT
Vacuum erection device (VED), used to treat radical prostatectomy (RP)-associated erectile dysfunction, has attracted considerable attention. However, the optimal negative pressure remains to be determined. This investigation explored the optimal pressure for VED therapy in penile rehabilitation. Thirty-six 9-week-old male rats were randomly divided into six groups: control groups (sham group, bilateral cavernous nerve crush [BCNC] group) and VED therapy groups (-200 mmHg group, -300 mmHg group, -400 mmHg group, -500 mmHg group). BCNC group and VED therapy groups underwent BCNC surgery. Intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was calculated to assess erectile function. Masson's trichrome (MT) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry, and real-time polymerase chain reaction (RT-PCR) were performed to explore cellular and molecular changes of the penis. Compared to the BCNC group, ICP/MAP ratios in all VED treatment groups were improved significantly (all P < 0.05), but there were no statistically significant differences among VED therapy groups. With increased pressure, complications gradually emerged and increased in frequency. Expression of molecular indicators, such as endothelial nitric oxide synthase (eNOS) and alpha-smooth muscle actin (α-SMA), increased after VED therapy, and hypoxia-inducible factor 1α (HIF-1α) and transforming growth factor beta (TGF-β) decreased. In addition, VED therapy improved the outcomes of MT and TUNEL assay. This investigation demonstrated a pressure of -200 mmHg in a rat model is optimal for VED therapy for penile rehabilitation after RP. No further benefits were observed with increased pressure, despite an increase in complications.