Fibrosis Of Corpus Cavernosum Research Articles

Caveolin-1 scaffolding domain peptide prevents corpus cavernosum fibrosis and erectile dysfunction in bilateral cavernous nerve injury-induced rats.

Corpus cavernosum (CC) fibrosis significantly contributes to post-radical prostatectomy erectile dysfunction (pRP-ED). Caveolin-1 scaffolding domain (CSD)-derived peptide has gained significant concern as a potent antagonist of tissue fibrosis. However, applying CSD peptide on bilateral cavernous nerve injury (BCNI)-induced rats remains uninvestigated. The aim was to explore the therapeutic outcome and underlying mechanism of CSD peptide for preventing ED in BCNI rats according to the hypothesis that CSD peptide may exert beneficial effects on erectile tissue and function following BCNI through limiting collagen synthesis in CC smooth muscle cells (CCSMCs) and CC fibrosis. After completing a random assignment of male Sprague Dawley rats (10 weeks of age), BCNI rats received either saline or CSD peptide treatment, as opposed to sham-operated rats. The evaluations of erectile function (EF) and succedent collection and histological and molecular biological examinations of penile tissue were accomplished 3weeks postoperatively. In addition, the fibrotic model of CCSMCs was used to further explore the mechanism of CSD peptide action in vitro. The assessments of EF, SMC/collagen ratio, α-smooth muscle actin, caveolin-1 (CAV1), and profibrotic indicators expressions were conducted. BCNI rats exhibited significant decreases in EF, SMC/collagen ratio, α-SMA, and CAV1 levels, and increases in collagen content together with transforming growth factor (TGF)-β1/Smad2 activity. However, impaired EF, activated CC fibrosis, and Smad2 signaling were attenuated after 3weeks of CSD peptide treatment in BCNI rats. In vitro, TGF-β1-induced CCSMCs underwent fibrogenetic transformation characterized by lower expression of CAV1, higher collagen composition, and phosphorylation of Smad2; then, the delivery of CSD peptide could significantly block CCSMC fibrosis by inactivating Smad2 signaling. Based on available evidence of CSD peptide in the prevention of ED in BCNI rats, this study can aid in the development and clinical application of CSD peptide targeting pRP-ED. This study provides data to suggest that CSD peptide protects against BCNI-induced deleterious alterations in EF and CC tissues. However, the available evidence still does not fully clarify the detailed mechanism of action of CSD peptide. Administration of CSD peptide significantly retarded collagen synthesis in CCSMCs, limited CC fibrosis, and prevented ED via confrontation of TGF-β1/Smad signaling in BCNI rats.

Combining transcriptomic analysis and network pharmacology to explore the mechanism by which Shaofu Zhuyu decoction improves diabetes mellitus erectile dysfunction

BackgroundErectile dysfunction is common among the complications of diabetes mellitus. Shaofu Zhuyu decoction (SFZYD) is commonly used to treat diabetic mellitus erectile dysfunction (DMED). However, its main active components and specific mechanism are still unknown. PurposeTo confirm the activity of SFZYD in improving DMED, explore the main active components of SFZYD, and clarify the underlying mechanism. MethodsA diabetic rat model was induced with streptozotocin (STZ). After intragastric administration, erectile function was assessed by the maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP). Corpus cavernosum fibrosis was evaluated by Masson staining, and ELISA methods were used to determine the serum levels of IL-6, TNF-α, IL-10, IL-4 and IL-1β to evaluate inflammation. Then, the main active components of SFZYD were identified by UPLC‒MS/MS. Finally, the target and biological mechanism of SFZYD in improving DMED were predicted by combined network pharmacology and transcriptomics, which was also validated by molecular docking and cellular thermal shift assay (CETSA) experiments. ResultsSFZYD significantly improved erectile dysfunction and inhibited inflammatory responses and local tissue fibrosis in diabetic rats. A total of 1846 active components were identified by UPLC‒MS/MS, and isorhamnetin was the main active component. The transcriptomic results were used to identify differentially expressed genes among the control, DM and SFZYD groups, and 1264 differentially expressed genes were obtained from the intersection. The network pharmacology results showed that SFZYD acts on core targets such as AKT1, ALB, HSP90AA1 and ESR1 through core components such as isorhamnetin, quercetin and chrysophanic acid. Further combined analysis revealed that multiple targets, such as CYP1B1, DPP4, NOS2 and LCN2, as well as the regulation of the PI3K-AKT signaling pathway, may be important mechanisms by which SFZYD improves DMED. Molecular docking verification showed that isorhamnetin, the key component of SFZYD, has good binding ability with several core targets, and its binding ability with CYP1B1 was the strongest. The CETSA results showed that isorhamnetin binds to CYP1B1 in CCECs. ConclusionSFZYD improves DMED, inhibits the inflammatory response and alleviates local tissue fibrosis. The combined application of transcriptomic, network pharmacology, molecular docking and CETSA approaches was helpful for revealing the mechanism by which SFZYD improves DMED, which may be related to the regulation of CYP1B1 and the PI3K-Akt signaling pathway.

Bradykinin B1 receptor antagonist protects against cold stress-induced erectile dysfunction in rats.

Erectile dysfunction (ED) demonstrates seasonal variation with higher rates in winter, and we hypothesize that endothelial damage in erectile tissue caused by bradykinin receptor B1 (B1R) might be detrimental to this change. To find out direct correlations between cold stress and ED, through which to further investigate the functional roles of B1R in erectile tissue and to elucidate the therapeutic roles of the B1R antagonist in a cold stress-induced ED rat model. Cold stress rat models are established through long-term intermittent exposure to low temperature. After their erectile function was assessed, ED rats were treated with the B1R antagonist through intraperitoneal injection. Penile tissues were obtained at the end of the experiment after measurement of intracavernosal pressure/mean arterial pressure (ICP/MAP); the location and distribution of cytokine expression were determined by immunohistochemistry; cytokine levels and NOS and CD31 expression were detected by Western blotting; and collagen fibers and smooth muscles were observed through Masson staining. Cold stress impairs erectile function, and the B1R antagonist protects against it. We observed decreased erection frequency, prolonged erection latency time, decreased ICP/MAP, overexpression of B1R, increased expression of cytokines on cavernous sinus endothelium, and increased levels of collagen fibers/smooth muscles on erectile tissue in response to cold stress. Also, NOS and CD31 expression was downregulated. B1R antagonist treatment shows enhanced erectile function through increased erection frequency, shortened erection latency time, and increased ICP/MAP. Also, it reduces collagen fibers/smooth muscles, TNF-α, TGF-β1, and IL-6 and upregulates the expression of nNOS and CD31. Our findings cast new light on the correlations between cold stress and erectile function and potential new applications of existing B1R antagonist drugs in the field of ED. Our data support that cold stress impairs erectile function. B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it, and B1R inhibition protects against fibrosis and endothelial damage. Other ways of B1R antagonist blocking methods in different types of ED still need to be investigated. Long-term intermittent cold stress impairs erectile function, and B1R-mediated, cytokine-induced corpus cavernosum fibrosis and endothelial damage might be the main reason behind it. B1R inhibition also protects against fibrosis and endothelial damage. Our data support the hypothesis that cold stress impairs erectile function and that B1R blockade ameliorates the symptoms of ED, possibly by reversing fibrosis and endothelial damage in erectile tissue.

Buyang Huanwu Decoction Ameliorates Damage of Erectile Tissue and Function Following Bilateral Cavernous Nerve Injury.

To verify the effect of Buyang Huanwu Decoction (BHD) in ameliorating erectile dysfunction (ED) after radical prostatectomy (RP). The composition of BHD was verified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) analysis. Bilateral cavernous nerve crush injury (BCNI) in rats was used to mimic the neurovascular injury occurring after RP. By the envelope method, forty rats were randomly divided into 4 groups as follows: sham (cavernous nerves exposed only), model (BCNI), low-dosage BHD [LBHD, 12.8 g/(kg·d)], and high-dosage BHD [HBHD, 51.2 g/(kg·d)] groups, 10 rats in each group, feeding for 3 weeks respectively. Erectile function was evaluated by measuring intracavernosal pressure (ICP). Changes in the histopathology of corpus cavernosum (CC) were examined by hematoxylin-eosin staining. Meanwhile, the fibrosis of CC was measured by Masson's trichrome staining and Western blot was used to detect the expressions of collagen I, transforming growth factor beta 1 (TGF- β 1) and α-smooth muscle actin (α-SMA). Apoptosis index was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and Western blot for determining the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). The oxidative stress in the CC were assessed by the superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) levels. The proteins expression of c-Jun N-terminal kinase (JNK) and c-Jun were detected by Western blot. In addition, the expression of α-SMA and p-c-Jun in the CC was observed by double immunofluorescence staining. The UPLC-QTOF-MS/MS analysis showed that BHD contained calycosin-7-O- β -D-glucoside, ononin, calycosin and formononetin. Compared with the model group, LBHD and HBHD treatment improved the ICP and the circumference, area, and weight of CC (P<0.05 or P<0.01). Furthermore, LBHD and HBHD treatments increased CC smooth muscle content and decreased apoptosis index (P<0.05 or P<0.01). LBHD and HBHD also elevated SOD and expression level of α -SMA and Bcl-2, and reduced MDA and ROS levels, as well as expression of TGF- β 1, collagen I, Bax, p-c-JNK, p-JNK in the CC compared with the model group (P<0.05 or P<0.01). The double immunofluorescence staining showed that the fluorescence degree of p-c-Jun in both LBHD and HBHD treatment groups was significantly reduced, whereas the α -SMA expression increased (P<0.05 or P<0.01). BHD can improve ED of rats with BCNI, which is related to inhibiting fibrosis, apoptosis, and oxidative stress of CC. The ROS/JNK/c-Jun signaling pathway may play an important role in the process.

JAK2 deficiency improves erectile function in diabetic mice through attenuation of oxidative stress, apoptosis, and fibrosis.

BackgroundJanus kinase 2 (JAK2) is activated in diabetic mellitus (DM) conditions and may enhance oxidative stress, apoptosis and fibrosis in many tissues. Whether JAK2 activation is involved in the occurrence of diabetic erectile dysfunction (ED) is unknown.ObjectivesWe performed this study to investigate the effect of JAK2 deficiency on diabetic ED.Materials and methodsConditional JAK2 gene knockout mice (Cre +/+‐JAK2fl/fl ) were used, in which JAK2 gene knockout could be induced by tamoxifen. Mice fell into four groups: control, JAK2 knockout (JAK2−/−), DM, and DM with JAK2−/−. DM was induced by intraperitoneal injection of streptozotocin. Two months later, JAK2 gene knockout was induced with tamoxifen in Cre+/+‐JAK2fl/fl mice. After another 2 months, erectile function was measured by electrical stimulation of the cavernous nerve, and penile tissues were harvested. Ratio of maximal intracavernosal pressure (MIP) to mean arterial blood pressure (MAP), expression and phosphorylation of JAK2, oxidative stress level, NO/Cyclic Guanosine Monophosphate (cGMP) pathway, apoptosis, fibrosis, and transforming growth factor beta 1 (TGF‐β1)/Smad/Collagen IV pathway in corpus cavernosum, were measured.ResultsJAK2 expression was remarkably decreased after induction with tamoxifen. JAK2 was activated in penile tissues of diabetic mice, and JAK2 deficiency could improve the impaired erectile function caused by DM. However, in mice without DM, JAK2 deficiency had no apparent influence on erectile function. Levels of oxidative stress, apoptosis, fibrosis, and TGF‐β1/Smad/Collagen IV pathway were all elevated by DM, whereas JAK2 deficiency lessened these alterations in diabetic mice. Moreover, JAK2 deficiency improved the expression of the down‐regulated NO/cGMP pathway in diabetic mice. In non‐diabetic mice, no apparent changes were found in aforementioned parameters after JAK2 gene knockout.Discussion and conclusionOur study showed that JAK2 deficiency could improve erectile function in diabetic mice, which might be mediated by reduction in oxidative stress, apoptosis, and fibrosis in corpus cavernosum.

Low androgen status inhibits erectile function by increasing pyroptosis in rat corpus cavernosum

The mechanism of erectile dysfunction (ED) caused by low androgen status is not fully understood. To investigate whether low androgen status inhibits erectile function of rats by inducing pyroptosis in the corpus cavernosum (CC). Thirty-six eight-weeks-old healthy male Sprague-Dawley rats were equally divided into six groups: sham-operated group (4w sham, 8w sham), castration group (4w cast, 8w cast), and castration + testosterone (T) group (4w cast + T, 8w cast + T). The rats in castration + T groups were injected with testosterone propionate subcutaneously every other day. After 4 and 8weeks, the ratio of maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP), the level of serum T, the concentration of nitric oxide (NO) and interleukin-1β (IL-1β), the expression of NOD-like receptor pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), Caspase-1 p20, gasdermin D-N (GSDMD-N), transforming growth factor β1 (TGF-β1), collagen-I, and collagen-III, the ratio of smooth muscle/collagen (SM/C), and the proportion of pyroptotic cells in the CC were analyzed. The ratio of ICPmax/MAP (3/5V) and SM/C, the level of NO and serum T was significantly decreased in castration groups when compared to other groups (p<0.01). NLRP3, ASC, Caspase-1, and GSDMD were mainly expressed in the cytoplasm of smooth muscle cells (SMCs) and endothelial cells (ECs) in the CC. The expression of NLRP3, ASC, Caspase-1p20, GSDMD-N, IL-1β, TGF-β1, collagen-I, and collagen-III was significantly increased in castration groups when compared with other groups (p<0.01). The proportion of pyroptotic cells in the CC was increased significantly in castration groups when compared with other groups (p<0.05). Low androgen status inhibits erectile function of rats by promoting CC fibrosis and reducing NO synthesis through pyroptosis of SMCs and ECs in the CC.

Simvastatin alleviated diabetes mellitus-induced erectile dysfunction in rats by enhancing AMPK pathway-induced autophagy.

Diabetes mellitus-induced erectile dysfunction is a common diabetic complication, and new therapeutics and the pathogenesis of diabetes mellitus-induced erectile dysfunction need to be investigated. The aim was to investigate the pathogenesis of diabetes mellitus-induced erectile dysfunction and the pharmacological mechanism of simvastatin treatment in diabetes mellitus-induced erectile dysfunction model rats. A total of 86 male Sprague Dawley rats aged 8weeks old were used in this study. The rats were divided into three groups: control (normal), diabetes mellitus-induced erectile dysfunction (streptozotocin-injected), and diabetes mellitus-induced erectile dysfunction+simvastatin (sim). Each group was subdivided into two subgroups for in vitro and in vivo analyses. A bioinformatics method was used to detect differences in gene expression in the corpus cavernosum between normal and diabetes mellitus-induced erectile dysfunction rats. Erectile function was measured by a cavernous nerve electrostimulation test. Corpus cavernosum fibrosis was assessed by Masson staining and Western blotting. Immunofluorescence and Western blotting were performed to explore the differential expression of autophagy-related genes and the AMPK-SKP2-CARM1 pathway genes in rat cavernous smooth muscle cells and the corpus cavernosum. The autophagosomes of the corpus cavernosum tissue were observed by transmission electron microscopy. Autophagy-related genes and pathways (the AMPK and FoxO pathway) were identified by bioinformatics analysis and confirmed at the protein level. Simvastatin, an AMPK agonist, was used to treat diabetes mellitus-induced erectile dysfunction rats for 8weeks, demonstrating that erectile function was improved for 80.5% (P<.05) of rats. Corpus cavernosum fibrosis was alleviated (P<.05), and autophagy was further enhanced (P<.05); these results might be partially caused by AMPK-SKP2-CARM1 pathway activation (P<.05). Simvastatin could enhance protective autophagy by activating the AMPK-SKP2-CARM1 pathway to improve erectile function in diabetes mellitus-induced erectile dysfunction rats.

Antioxidant Mechanism of Xiaojin Pill () for Treatment of Peyronie's Disease in Rats Based on Matrix Metalloproteinases.

To evaluate the effects of Xiaojin Pill () in the treatment of Peyronie's disease (PD) in a rat model. Twenty-four male Sprague-Dawley rats were randomly divided into four groups with 6 in each: sham operation, PD model, vehicle control and Xiaojin Pill groups. The rats in the sham operation group received penile tunica albsginea (TA) injection with 50 μL vehicle, while the rats in the other 3 groups received 50 μL penile TA injection of 50 μg transforming growth factor (TGF)-β1. Forty-two days after the injection, rats in the vehicle control and Xiaojin Pill groups received 0.5 mL water and Xiaojin Pill solution (107 mg/kg of body weight), respectively by gavage for 28 days, while those in the sham operation and PD model groups did not receive any intervention. After intervention, the expressions of matrix metalloproteinase 2/9 (MMP2/9), nitric oxidesynthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. Rats in the PD model and vehicle control groups presented obvious fibrosis in corpus cavernosum (CC) and demonstrated a significantly increased expressions of MMP2 and MMP9 in the CC compared with the sham operation group (all P<0.01). In contrast, the expressions of MMP2 and MMP9 in the Xiaojin Pill group were significantly down-regulated (both P<0.01). In addition, the levels of NOS and MDA in CC were significantly increased while the activity of SOD was decreased in the PD model and vehicle control groups compared with the sham operation group (all P<0.01). After Xiaojin Pill treatment, the levels of MDA, NOS and SOD appeared to be corrected (all P<0.01). Xiaojin Pill could reduce fibrosis in the CC by decreasing the expressions of MMPs, NOS and MDA, and by increasing the activity of SOD. Therefore, Xiaojin Pill might be a therapeutic option for PD.

Islet transplantation improved penile tissue fibrosis in a rat model of type 1 diabetes

BackgroundGlycaemic control is one of the most effective strategies for the treatment of diabetes-related erectile dysfunction (DMED). Compared to conventional anti-diabetic drugs and insulin, islet transplantation is more effective in the treatment of diabetic complications. The aim of this study was to investigate the efficacy of islet transplantation for reversing advanced-stage DMED in rats and to observe its influence on corpus cavernosum fibrosis.MethodsWistar rats were intraperitoneally injected with streptozotocin to establish a diabetes model. After 12 weeks, the rats were divided into 4 groups: diabetic, insulin, islet transplantation, and normal control. Following supplementation, the changes in blood glucose and weight were determined sequentially. Penile erectile function was evaluated by apomorphine experiments in the fourth week, and the penile corpus cavernosum was also collected for assessment by Masson staining, immunohistochemistry and Western blot to observe the spongy tissue and the related cellular changes at the molecular level.ResultsIslet transplantation significantly ameliorated penile erectile function in advanced-stage diabetic rats. The ratio of corpus cavernosum smooth muscle cells to fibroblasts and the expression level of α-SMA in the islet transplantation group were significantly higher than those in the diabetic and insulin groups. In addition, the expression levels of TGF-β1, p-Samd2, and connective tissue growth factor (CTGF) in the islet transplantation and insulin groups were much lower than those in the diabetic group, while those in the islet transplantation group were significantly lower than those in the insulin group.ConclusionsOur findings strongly suggest that islet transplantation can promote the regeneration of smooth muscle cells and ameliorate corpus cavernosum fibrosis to restore its normal structure in advanced-stage diabetic rats. The possible mechanism of ameliorating corpus cavernosum fibrosis by islet transplantation may be associated with improvement of the hyperglycaemic status in diabetic rats, thereby inhibiting the TGF-β1/Samd2/CTGF pathway.

Effect of lysyl oxidase (LOX) on corpus cavernous fibrosis caused by ischaemic priapism.

Penile fibrosis caused by ischemic priapism (IP) adversely affects patients’ erectile function. We explored the role of lysyl oxidase (LOX) in rat and human penes after ischemic priapism (IP) to verify the effects of anti‐LOX in relieving penile fibrosis and preventing erectile dysfunction caused by IP in rats. Seventy‐two rats were randomly divided into six groups: control group, control + β‐aminopropionitrile (BAPN) group, 9 hrs group, 9 hrs + BAPN group, 24 hrs group, and 24 hrs + BAPN group. β‐aminopropionitrile (BAPN), a specific inhibitor of LOX, was administered in the drinking water. At 1 week and 4 weeks, half of the rats in each group were randomly selected for the experiment. Compared to the control group, the erectile function of IP rats was significantly decreased while the expression of LOX in the corpus cavernosum was significantly up‐regulated in both 9 and 24 hrs group. Proliferated fibroblasts, decreased corpus cavernosum smooth muscle cells/collagen ratios, destroyed endothelial continuity, deposited abnormal collagen and disorganized fibers were observed in IP rats. The relative content of collage I and III was not obviously different among the groups. β‐aminopropionitrile (BAPN) could effectively improve the structure and erectile function of the penis, and enhance recovery. The data in this study suggests that LOX may play an important role in the fibrosis of corpus cavernosum after IP and anti‐LOX may be a novel target for patients suffering with IP.

Transplantation of adipose tissue-derived stem cell-derived exosomes ameliorates erectile function in diabetic rats.

Mesenchymal stem cells (MSCs) have been considered as an attractive tool for the therapy of diseases. Accumulating evidence indicates that the healing effects of MSCs are mainly related to paracrine action rather than transdifferentiation. Exosomes excreted from MSCs have emerged as physiologically relevant and powerful components of the MSC secretome. However, whether MSC-derived exosomes can improve erectile function of streptozotocin-induced diabetic rats and its mechanism remains unknown. Our previous work showed that adipose tissue-derived stem cells (ADSCs) transplantation could increase endothelial and smooth muscle contents and improve erectile function of diabetic rats. In this study, ADSC-derived exosomes (ADSC-Exo) exhibited in vitro proangiogenic properties, induced the proliferation of endothelial cells and restored erectile function in vivo, as well as decreased fibrosis of corpus cavernosum. In further experiments, we found that ADSC-Exo contained some proangiogenic (miR-126, miR-130a and miR-132) microRNAs and an antifibrotic microRNA family (miR-let7b and miR-let7c). Thus, it is reasonable to postulate that ADSC-Exo transports key functional miRNAs to target cells in a specific manner to improve functional recovery or to activate endogenous repair mechanisms. This proof-of-concept study provides a novel approach for the treatment of diabetic erectile dysfunction.

BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells promote erectile function in a rat model of cavernous nerve electrocautery injury.

Erectile dysfunction (ED) continues to be a significant problem for men following radical prostatectomy. We hypothesize that intracavernous injection of BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) can ameliorate ED in a rat model of cavernous nerve electrocautery injury (CNEI). Forty-two male Sprague-Dawley rats were randomly divided into four groups: sham + PBS (n = 6), CNEI + PBS (n = 12), CNEI + hUCB-MSCs (n = 12) and CNEI + BDNF-hUCB-MSCs (n = 12). At day 28 post-surgery, erectile function was examined and specimens were harvested for histology. Immunofluorescence staining, Masson's trichrome staining and transmission electron microscopy were performed to determine the structural changes in corpus cavernosum. Cells that are injected into penis were labeled by BrdU and tracked by immunofluorescence staining. Three days post-surgery, the concentration of BDNF protein in penile tissues was measured by Western blotting. Rats intracavernosally injected with BDNF-hUCB-MSCs showed the most significant improvement in the ratio of maximal ICP to MAP (ICP/MAP). Histological examinations showed moderate recovery of nNOS-positive nerve fibers, ratio of smooth muscle to collagen and smooth muscle content in the CNEI + hUCB-MSCs group and remarkable recovery in the CNEI + BDNF-hUCB-MSCs group compared to the CNEI + PBS group. By TEM examination, atrophy of myelinated and non-myelinated nerve fibers was noted in CNEI + PBS group and significant recovery was observed in two treated groups. There were more BrdU-positive cells in the BDNF-hUCB-MSCs group than in the hUCB-MSCs group both in the penis and in the MPG. Three days post-surgery, the concentration of BDNF protein in penile tissues in BDNF-hUCB-MSCs group was much higher than in other groups. Intracavernous injection of BDNF-hypersecreting hUCB-MSCs can enhance the recovery of erectile function, promote the CNs regeneration and inhibit corpus cavernosum fibrosis after CNEI in a rat model.

Therapeutic potential of human umbilical cord blood mesenchymal stem cells on erectile function in rats with cavernous nerve injury.

To evaluate the therapeutic potential of human umbilical cord blood mesenchymal stem cells (hUCBMSCs) on promoting erectile function in a rat model of bilateral cavernous nerve (CN) crush injury. Fifty male Sprague-Dawley rats were randomly assigned to sham + PBS group (n = 10), BCNI (bilateral cavernous nerve crush injury) + PBS group (n = 10), BCNI + hUCBMSCs group (n = 30). At day 28 (n = 10) post-surgery, erectile function was examined and histological specimens were harvested. Compared with BCNI + PBS group, hUCBMSC intracavernous injection treatment significantly increased the mean ratio of ICP/MAP, nNOS-positive nerve fibers in the dorsal penile nerve, smooth muscle content, and smooth muscle to collagen ratio in the corpus cavernousum. Electron microscopy revealed few CN and major pelvic ganglion (MPG) lesions in the BCNI + hUCBMSCs group. Injected hUCBMSCs were localized to the sinusoid endothelium of the penis and MPG on day 1, 3, 7, and 28 post-intracavernous injection. hUCBMSCs intracavernous injection treatment improves erectile function by inhibiting corpus cavernosum fibrosis and exerting neuroregenerative effects on cell bodies of injured nerves at MPG in a BCNI rat model.

Early chronic low-dose tadalafil administration prevents corporal fibrosis following cavernous nerve injury in rats

Objective To investigate the preventive effect of early chronic tadalafil administration on corporal fibrosis induced by cavernous nerve injury (CNI) in rats.Methods Thirty-six male SpragueDawley rats were randomly divided into three groups:no CNI (sham,n =12),bilateral CNI exposed to either no tadalafil (CN crush,n =12) or tadalafil (treatment,n =12) at a dose (2 mg/kg) daily postoperation for 4 weeks.At the time point,we assessed erectile function by apomorphine test.Then immunohistochemical antibody staining was performed for transforming growth factor-β1 (TGF-β1).And the Masson staining was used to quantitatively analyze the ratio of smooth muscle to collagen fibers in corpus cavernosum.Results Penile erection was observed in 54.55％ (6/11) of the rats for (1.12 ± 0.81) times within 30 min in treatment group,as compared with 0％ (0/11) of the rats for (0.00 ±0.00) time in CN crush group (P＜0.05),and 100％ (12/12) oftherats for (2.11 ±0.86) time in sham group (P＜0.05).The expression of TGF-β1 was significantly weaker in treatment group than in CN crush group (14.12 ±3.72 vs.26.45 ± 5.33,P ＜ 0.05).The ratio of smooth muscle to collagen fibers in corpus cavernosum in treatment group was significantly higer than that in CN crush group (0.31 ± 0.08 vs.0.20 ± 0.05,P ＜0.05).Conclusion Early chronic low-dose tadalafil administration can improve fibrosis of corpus cavernosum induced by CNI and contributes to restoration of erectile function. Key words: Canvernous nerve; Crush; Erectile dysfunction; Tadalafil; Rat

Long-term efficacy and safety of self-intracavernous injection of prostaglandin E1 for treatment of erectile dysfunction in China

The study evaluated the long-term efficacy and safety profiles of self-intracavernous injection of prostaglandin E1 (PGE1) for erectile dysfunction (ED). Four hundred and sixteen ED patients were treated with self-intracavernous injection of PGE1 from January 1998 to December 2007 in our outpatient service. Follow-up was made to investigate the efficacy and side effects of this treatment. It was found that 261 patients (62.7%) felt satisfied and kept using this treatment due to its advantages of satisfactory efficacy and reasonable expense. Twenty-seven of them (6.5%) got rid of PGE1 treatment after five times injections and did not need any other drugs to maintain satisfactory sexual lives. Two hundred and fourteen (51.4%) patients kept using this treatment for over 1 year, 26 (6.2%) over 5 years, 12 (2.9%) over 8 years and 7 (1.7%) over 10 years. The major complications of self-intracavernous injection of PGE1 include fibrosis of corpus cavernosum (three cases), ecchymosis associated with vascular injury due to injection (23 cases) and pain associated with injection (295 cases). There were no patients displaying priapism. It is concluded that self-intracavernous injection of PGE1 is a safe and effective treatment for ED with various aetiologies and a broad range of severity, and no serious complications were observed after long-term application.

1541 DISTAL CORPUS CAVERNOSUM SMOOTH MUSCLE FIBROSIS DUE TO NON-ISCHAEMIC PRIAPISM- SHOULD EMBOLISATION BE PERFORMED EARLIER?

INTRODUCTION AND OBJECTIVES: Non-ischaemic priapism is due to unregulated cavernous arterial inflow. Although rare, it is commonly associated with perineal or penile trauma. Since the venous outflow mechanism is unaffected the corpus cavernosum is perfused with oxygenated blood and therefore these patients can be managed conservatively. We report on our series of patients with non-ischaemic priapism who have developed fibrosis of the distal corpus cavernosum following a period of conservative treatment. METHODS: Over a 5 year period, 7 patients with non-ischaemic priapism presented to our unit. The mean age was 37.4 years (range 20 56). The etiology in 6 cases was secondary to a perineal injury and in 1 case conversion of an ischaemic priapism to a non ischaemic priapism following surgical intervention. The diagnosis of non-ischaemic priapism in all patients was based on the clinical history and examination, cavernosal blood gas analysis, colour duplex ultrasonography of the penis and pudendal angiography. 4 cases (57%) also underwent a penile MRI. RESULTS: Although the diagnostic tests confirmed non-ischaemic priapism, follow up Doppler studies and MRI penis showed the development of distal corpus cavernosum fibrosis. Pudendal artery super selective embolization was eventually performed in all of the patients, of which 2 (28.5%) patients underwent a second attempt at embolisation. On follow up these patients reported the development of erectile dysfunction due to poor distal penile tumescence in all cases and the penile MRI demonstrated distal corpus cavernosum fibrosis. Four patients (57%) eventually underwent insertion of a penile implant due to failed pharmacotherapies. A further 3 (43%) patients are using PDE-5 inhibitors. The conditions were reproduced in an in vitro model using precontracted strips of rabbit corpus cavernosum superfused at high pO2 levels. This showed that the smooth muscle tone reduced by 43% of the initial tone (n 4) after superfusion for 12 hours indicating irreversible smooth muscle dysfunction. CONCLUSIONS: The risk of ischaemic damage in non-ischaemic priapism is expected to be minimal due to the oxygenation of the corpus cavernosum being maintained. However, corpus cavernosum perfusion with higher than normal pO2 levels may result in oxidative stress due to the formation of reactive oxygen species (ROS). Irreversible damage to the smooth muscle is followed by the development of fibrosis, Based on these findings we suggest that superselective embolisation of these cases should be performed at the earliest opportunity.

Al‐Ghorab Shunt Plus Intracavernous Tunneling for Prolonged Ischemic Priapism

To investigate the efficacy and safety of the corpus cavernosum-corpus spongiosum shunt (Al-Ghorab Shunt) plus intracavernous tunneling (CC-CSS+ICT) for prolonged ischemic priapism (PIP). Twelve patients with PIP were enrolled in this study. The mean age of patients was 38.3 ± 9.2 years old and the mean duration of PIP was 2.8 ± 1.0 days (range, 1.5-4 days). All patients received CC-CSS+ICT for treating PIP. The penile hardness score (PHS) and pain visual analogue score (PVAS) were used to assess the efficacy of the surgery 1, 3, and 5 days after surgery. Color duplex Doppler ultrasonography, International Index of Erectile Function, and quality of life (QOL) were used for evaluating penile morphology, erectile function, QOL, and response to sildenafil treatment. The mean duration of follow up was 21.6 ± 10.1 months. Penile detumescence was successfully restored for all 12 patients postsurgery, with the mean PHS and PVAS significantly decreased compared with that presurgery at different time points (1, 3, 5 days postsurgery; P < .001). The cavernosal arterial blood flow observed with the mean PSV at 1, 3, and 5 days postoperation were 17.79 ± 2.04, 19.14 ± 1.58, and 7.73 ± 2.02 cm/s respectively. All patients suffered from corpus cavernosum fibrosis and erectile dysfunction postoperation; only 2 cases (16.7%) with a short duration of PIP (1.5 days) showed response to sildenafil treatment, and 3 cases (25.0%) with severe fibrosis were satisfied with sexual life after excision of penile corpus cavernosum scar and penile prosthesis implantation. The CC-CSS+ICT could quickly reduce penile rigidity and pain for improving the symptoms of PIP and suggests a safe and effective therapeutic method for PIP.

Outcome of implanting penile prosthesis for treating erectile dysfunction: experience with 42 cases

To report a short-time result of three-piece inflatable penile prosthesis (IPP) implantation on treating patients with organic erectile dysfunction (ED). Three-piece IPPs were implanted in 42 Chinese patients with ED refractory to systemic treatment between May 2002 and May 2004. The etiologies of ED were neurogenic (28 with paraplegia and seven with traumatic nervi-erigentes injury); congenital venous leakage (5 cases), fibrosis of corpus cavernosum (1case) and Klinefelter's syndrome (1 case). The follow-up period ranged from 24 to 57 months. Implantation procedures were successfully performed upon all 42 patients. The length of implanted prosthesis was from 13 cm to 18 cm, and the diameter was 1 cm. The implanted prosthesis was made by the Medical Instrumentation Company of Muping (Muping, Shandong, China). Localized infection occurred in only one patient and mechanical complications occurred in five patients. Coitus could be performed in 41 cases (97.6%). Three patients with congenital venous leakage made their spouses pregnant after implantation. Implantation of three-piece IPP is an effective and safe modality for treating patients with ED. It can be well accepted by Chinese patients because of its efficacy.

Priapismo de alto flujo en el contexto de una enfermedad oncológica sistémica

We present the case of a 21-year-old man with a 2-month history of high-flow priapism and no antecedents of direct perineal trauma. Relevant history included Raynaud's disease without current treatment. Cavernous body gasometry was performed. Intracavernous phenylephrine injection was unsuccessful. Selective arteriography of the internal pudenda with selective unilateral embolization with autologous coagulation was unsuccessful due to early recanalization. The priapism was resolved by perfusion of 30 ml of phenylephrine at a concentration of 10 μg/ml. During follow-up, the patient developed bulbourethral-membranous stenosis and erectile dysfunction secondary to corpus cavernosum fibrosis. Tumoral disease was ruled out by imaging tests. Six months later, the patient was diagnosed with primary monophasic pulmonary sarcoma and subsequently with poorly differentiated oral epidermoid carcinoma. We highlight the poor outcome of priapism with corpus cavernosum fibrosis, even though this entity is not associated with changes due to acidosis or potential tissue injury. We also stress the temporal association of the development of two distinct, highly aggressive neoplastic processes, although prior studies showed no clinical or radiological evidence of malignancy that would warrant a diagnosis of paraneoplastic syndrome.

Platelet-derived growth factor (PDGF) and PDGF receptors in rat corpus cavernosum: changes in expression after transient in vivo hypoxia.

Platelet-derived growth factor (PDGF) overactivity has been implicated in atherosclerosis and several fibrotic conditions including lung and kidney fibrosis, liver cirrhosis and myelofibrosis. Low oxygen tension (hypoxia) is a known stimulus for transcriptional induction of PDGF ligand and receptor genes in different tissues. We studied the expression and localization of PDGF-A, PDGF-B, and PDGF receptor (PDGFR)-alpha and -beta subunits in adult rat isolated corpus cavernosum (CC) under generalized transient hypoxia (pO(2) 10%) in comparison with normoxic conditions. Semi-quantitative RT-PCR analysis of mRNA extracted from rat penis showed higher amounts of PDGF-A, PDGF-B and PDGFR-beta mRNA transcripts in hypoxic versus normoxic animals. The immunohistochemical analysis showed that the localization of PDGF subunits and PDGFR-beta was confined to the cytoplasm of the perivascular smooth muscle cells, endothelium and trabecular fibroblasts. Our findings indicate that transient low oxygen tension induces PDGF overexpression in rat CC, which in the long term may lead to an increase of connective tissue production. We suggest that a local impairment of the PDGF/PDGFR system may contribute to CC fibrosis, which is an established cause of erectile dysfunction in man.