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
Penile length shortening and erectile dysfunction are common complications after radical prostatectomy. Various methods have been used to maintain erectile function, but less attention has been paid to preserving penis length. N-acetylcysteine (NAC) has the effect of antioxidation and antifibrotic, which may be beneficial to improve those postoperative complications. This study investigated the effect of NAC on maintaining the penile length and the erectile function after bilateral cavernous nerve crush (BCNC) and its underlying mechanism. Twenty-four male rats were randomly divided into three groups: control group, BCNC group, and BCNC + NAC group. NAC or equal volume of saline was daily administrated by intragastric gavage for 4 weeks. The initial and end penile lengths were measured. Intracavernosal pressure/mean arterial pressure (ICP/MAP) ratio was calculated to assess erectile function. Hematoxylin-eosin staining, Masson's trichrome staining, immunohistochemistry, and Western blot were performed to explore cellular and molecular changes of the penis. Compared to the BCNC group, the penile length, ICP/MAP ratio and smooth muscle/collagen ratio in the BCNC + NAC group were improved significantly (all P < 0.05), and the expressions of endothelial nitric oxide synthase, α-smooth muscle actin, glutathione, and glutathione peroxidase 1 were significantly increased after NAC treated (all P < 0.05), along with the decreased expressions of hypoxia-inducible factor-1α, transforming growth factor-β1, collagen I, collagen III, collagen IV, malonaldehyde, and lysine oxidase (all P < 0.05). This study demonstrated that NAC could maintain penile length and partly improve erectile function. Possible mechanism is directly and/or indirectly related to antihypoxic and antifibrosis.
ABSTRACT
<p><b>AIM</b>To prepare the mitoxantrone long circulating liposomes (LCL) and to observe the residence behavior of the mitoxantrone LCL in rabbits.</p><p><b>METHODS</b>The long circulating mitoxantrone liposomes were prepared by ethanol injection combined with the ammonium sulphate gradients method. Amphipathic polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE) was added to modify the membrane of the liposomes. The column-switching system of RP-HPLC was utilized to determine mitoxantrone concentration in rabbit plasma.</p><p><b>RESULTS</b>The mean diameter of the long circulating mitoxantrone liposomes was 60 nm, with the entrapping efficiency of 93.6%. With the same dosage (2 mg.kg-1) i.v. in rabbits, the mean residence time (MRT) of the long circulating mitoxantrone liposomes was 9.8 h, while that of the normal liposomes was 3.6 h, and the AUC of the former is 6.4 fold greater than of the latter. It showed that the long circulating mitoxantrone liposomes prolonged the resident time of the drug in the blood circulating system and they reduced the uptake by the reticuloendothelial system, simultaneously.</p><p><b>CONCLUSION</b>Liposomes with high entrapping efficiency and small particle size could be prepared by ethanol injection combined with the ammonium sulphate gradients method, and the liposomes modified by PEG-DSPE could raise the AUC and prolonged the resident time of the drug in the blood circulating system.</p>