Molecular mechanisms of vacuum therapy in penile rehabilitation: a novel animal study.

Penile rehabilitation (PR) is widely applied after radical prostatectomy. Vacuum erectile device (VED) therapy is the one of three PR methods used in the clinical setting that improve erectile function (EF) and is the only PR method which may preserve penile length. However, its unknown mechanism hampered doctors' recommendations and patients' compliance. To assess the effects of VED therapy on erectile dysfunction (ED) in a rat model of bilateral cavernous nerve crush (BCNC) and to investigate the molecular mechanism of VED in postprostatectomy ED. This was an experimental study using Sprague-Dawley rats in three groups: sham, BCNC, and BCNC plus VED. Intervention included BCNC, electrical stimulation of the cavernous nerve (CNS), and VED therapy. At the end of a 4-wk period, CNS was used to assess EF by maximum intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio and duration (area under the curve [AUC]). For the structural analyses, whole rat penis was harvested. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay was used for the assessment of apoptotic indices (AI). Immunohistochemistry was performed for endothelial nitric oxide synthase (eNOS), α-smooth muscle actin (ASMA), transforming growth factor beta 1 (TGF-β1), and hypoxia inducible factor-1α (HIF-1α). Staining for Masson's trichrome was utilized to calculate the smooth muscle/collagen ratios. EF was improved with VED therapy measured by ICP/MAP ratios and AUC. VED therapy reduced HIF-1α expression and AI significantly compared with control. Animals exposed to VED therapy had decreased TGF-β1 expression, increased smooth muscle/collagen ratios, and preserved ASMA and eNOS expression. To our knowledge, this is the first scientific study to suggest that VED therapy in the BCNC rat model preserves EF through antihypoxic, antiapoptotic, and antifibrotic mechanisms.

Yuan J ，Lin H ，Li P ，Zhang R ，Luo A ，Berardinelli F ，Dai Y ，Wang R ... -  《-》

COX-2-10aa-PGIS gene therapy improves erectile function in rats after cavernous nerve injury.

Erectile dysfunction (ED) is a very common complication after radical prostatectomy. COX-2-10aa-PGIS is a newly engineered protein with COX-2 and prostacyclin synthase activities that converts arachidonic acid directly to prostacyclin (prostaglandin I2 [PGI2]). PGI2 is a potent smooth muscle relaxant. The purpose of this study was to explore the effect and mechanism of COX-2-10aa-PGIS gene therapy in penile rehabilitation. Bilateral cavernous nerve crush (BCNC) in adult Sprague-Dawley rats was used to mimic radical prostatectomy-induced ED. Sprague-Dawley rats were randomly assigned into four groups: 1. sham surgery; 2. BCNC; 3. BCNC + null control recombinant adenovirus intracavernous injection; and 4. BCNC + Ad-COX2-10aa-PGIS intracavernous injection. Twenty-eight days later, intracavernosal pressure (ICP) was recorded under cavernous nerve stimulation; in the meantime, the mean arterial pressure (MAP) was monitored. At the end of the measurement, the penis was harvested and processed for (i) immunohistochemistry analysis of endothelial nitric oxide synthase (eNOS), alpha-smooth muscle actin (α-SMA), and transforming growth factor beta-1 (TGF-β1); (ii) Masson's trichrome stain for smooth muscle/collagen ratios; (iii) Western blot of eNOS, α-SMA, TGF-β1, and COX2-10aa-PGIS; and (iv) terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis. Erectile function was evaluated by ICP/MAP. Smooth muscle and endothelium functions in corpora cavernosum were assessed by Masson's trichrome stain, immunohistochemistry, and Western blot. Apoptosis was identified by TUNEL assay. The results were the following: 1. COX2-10aa-PGIS gene therapy improved erectile function (82%, compared with control) in the BCNC rat model; 2. COX2-10aa-PGIS gene therapy increased eNOS (121%) and α-SMA (118%) expression and decreased TGF-β1 (45%) expression; 3. COX2-10aa-PGIS gene therapy reduced cell apoptosis after cavernous nerve injury (64%); and 4. COX2-10aa-PGIS gene therapy improved smooth muscle/collagen ratios (81%). Our data demonstrated that COX2-10aa-PGIS improved erectile function after cavernous nerve injury through antifibrotic and anti-apoptotic mechanisms.

Lin H ，Yuan J ，Ruan KH ，Yang W ，Zhang J ，Dai Y ，Wang R ... -  《-》

Optimal pressure in penile rehabilitation with a vacuum erection device: evidence based on a rat model.

Yang XL ，Yang Y ，Fu FD ，Wu CJ ，Qin F ，Yuan JH ... -  《-》

N-acetylcysteine maintains penile length and erectile function in bilateral cavernous nerve crush rat model by reducing penile fibrosis.

Ma M ，Wu CJ ，Zhang P ，Li T ，Wei SZ ，Yu BT ，Qin F ，Yuan JH ... -  《-》

Optimal vacuum erectile device therapy regimen for penile rehabilitation in a bilateral cavernous nerve crush rat model.

Vacuum erectile device (VED) therapy has been widely used in penile rehabilitation after radical prostatectomy; however, there is no consensus on the best regimen. To explore an optimal VED therapy regimen in bilateral cavernous nerve crush (BCNC) rat model. Adult male rats were used to measure the effects of different durations (1-30 min) of VED treatment on penile length, penile blood gas analysis, and adverse effects. Forty-eight adult male rats were randomly divided into Sham, BCNC, and VED treatment groups (2-3-2-3 min, 4-3-3 min, 5-5 min, and 10 min). Penile length, erectile function, and side effects were detected after VED treatment. Histopathological staining and Western blotting were performed to explore the cellular and molecular changes. Prolongation of the duration of VED treatment significantly decreased the penile oxygen saturation, partial oxygen pressure, and arterial blood ratio (P < 0.05). Compared with the BCNC group, all VED treatment regimens partially reversed BCNC-induced penile shortening and erectile dysfunction (P < 0.0001), with the 4-3-3-min and 5-5-min treatment groups exhibiting more significant improvement than the 10-min and 2-3-2-3-min treatment groups (P < 0.0001). The mechanism may be related to the up-regulation of the smooth muscle cell/collagen ratio, endothelial nitric oxide synthase, and α-smooth muscle actin (all P < 0.0001); and the down-regulation of hypoxia-inducible factor-1α, transforming growth factor-β1, and apoptosis (all P < 0.0001). The incidence of adverse effects in the 2-3-2-3-min treatment group was the highest. The commonly used VED therapy regimens maintained erectile function and penile length of BCNC rat by relieving hypoxia and fibrosis, and no further benefits were observed with increased treatment frequency or prolonged treatment duration. Two consecutive 5-min treatments with a short interval is the optimal VED therapy regimen for penile rehabilitation in BCNC rat model.

Ma M ，Qin F ，Wu C ，Xiong W ，Yu B ，Wei S ，Huang C ，Xu J ，Yang X ，Yuan J ... -  《-》