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This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague-Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg
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Structural alterations in fibroelastic components of the penile corpus cavernousum (CC) may impair its compliance, resulting in venous leakage and erectile dysfunction (ED). Our study evaluated the effectiveness of noninvasive two-dimensional shear-wave elastography (2-D SWE) in quantifying penile CC lesions in rabbits with hyperlipidemia-induced ED. A total of 12 New Zealand white rabbits were randomly divided into two groups. Six were fed a high-cholesterol diet containing 2% cholesterol and 8.5% lard for 10 weeks and the other six were fed normal diet as controls. We measured the shear-wave elastic quantitative (SWQ) value of penile CC by 2-D SWE. Erectile function was investigated by intracavernous injection of papaverine, and immunohistochemical (IHC) staining and the western blot analysis to determine the penile CC lesions. After 10 weeks, the SWQ values obtained from penile CC were remarkably higher in the high-cholesterol-fed compared with the control group, and the ΔICP (ICP plateau minus ICP baseline)/MAP (ICP: intracavernous pressure, MAP: mean arterial pressure) was markedly decreased. The IHC staining and western blot revealed extracellular matrix (ECM) accumulation in penile cavernous tissues, and the smooth muscle cell (SMC) phenotypic transition was affected, as indicated by reduced alpha-smooth muscle actin and calponin-1 expression and increased phospho-myosin light chain20 (p-MLC20)/MLC20 and osteopontin expression. Hyperlipidemia resulted in ECM accumulation accompanied with SMC phenotypic transition in penile CC and impaired the erectile function eventually. These might, in turn, lead to variations in the SWQ values. It suggests that 2-D SWE may be a novel, noninvasive and effective approach that distinguishes penile CC lesions secondary to hyperlipidemia from normal.
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Objective: To explore of value of real-time shear wave elastography (SWE) in quantitative evaluation of corpus cavernosum hardness. Methods: Totally 150 healthy volunteers were divided into 5-12 years old group, 13-18 years old group, 19-30 years old group, 31-50 years old group and 51-70 years old group. Young's modulus of the corpus cavernosum was measured quantitatively with SWE imaging function. Results: The hardness of penile cavernosum increased with the increase of age. Young's modulus was (9.05±0.85)kPa in 5-12 years old group, (11.01±1.34)kPa in 13-18 years old group, (12.03±0.85)kPa in 19-30 years old group, (16.33±1.56)kPa in 31-50 years old group and (24.46±1.81)kPa in 51-70 years old group. Conclusion: SWE can be used for quantitative measurement of Young's modulus of corpus cavernosum, which is noninvasive, simple, safe and has important clinical application value.
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Objective@#To explore the treatment of penile incarceration with a metal ring.@*METHODS@#Based on our experience in the successful management of a case of penile incarceration with a metal ring by coiling and bloodletting from the corpus cavernosum, we reviewed the relevant literature and analyzed the indications, advantages and disadvantages of different methods for the treatment of penile incarceration with a circular foreign body.@*RESULTS@#The clamping and cutting methods were non-invasive, fast, effective, and with few complications, which could be applied to the treatment of penile strangulation at all levels. However, clamping was not desirable enough for a hard metal ring and the cutting method took a longer time and might increase the risk of unnecessary damage to the penile skin, urethra and cavernous body. Prepuce edema decompression and the thin tube-coiling method, with the advantages of minimal invasiveness, simple operation and no need of special tools, were suitable for penile strangulation injury under level 3, but might cause penile skin injury and potential postoperative erectile dysfunction. Surgical resection, as an invasive procedure, could be applied to severe penile strangulation at level 4 or 5.@*CONCLUSIONS@#The principle for the treatment of penile incarceration with a circular foreign body is to remove the foreign object as soon as possible and not to add secondary damage.
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Humans , Male , Bloodletting , Methods , Constriction, Pathologic , Therapeutics , Erectile Dysfunction , Foreign Bodies , Therapeutics , Jewelry , Penis , Wounds and Injuries , Pathology , Postoperative Complications , UrethraABSTRACT
<p><b>OBJECTIVE</b>This study investigated the effects of aqueous leaf extract of Tridax procumbens (ALETP) on contractile activity of corpus cavernosum in N-nitro-l-arginine methyl ester (l-NAME)-induced hypertensive male rats.</p><p><b>METHODS</b>Twenty normal, adult male rats (130-150 g) were divided into four groups of five rats each. Group I (control) was given normal saline (0.6 mL/kg) and group II was given l-NAME (40 mg/kg) for 6 weeks. Groups III and IV also received l-NAME (40 mg/kg) for 6 weeks but were further co-treated with 100 and 200 mg/kg of ALETP, respectively, from week 4 to week 6. All treatments were given orally. Strips of corpus cavernosum from each of the four groups were exposed to increasing concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP) (10-10mol/L) after contraction with phenylephrine (10 mol/L) to test for a dose-response effect. Response to potassium and calcium was also measured after cumulatively adding potassium and calcium (10-50 mmol/L) to potassium- and calcium-free organ chamber. Isometric contractions were recorded through an Ugo Basile data capsule acquisition system.</p><p><b>RESULTS</b>Mean arterial blood pressure was significantly reduced in the ALETP co-treated group compared to the control and l-NAME-only groups (P < 0.05). Cavernosa strips from ALETP co-treated rats exhibited significant inhibition of contraction in response to phenylephrine, potassium chloride, and calcium chloride (P < 0.05). Relaxation in response to Ach and SNP was also significantly impaired in cavernosa strips from the l-NAME-only treated group (P < 0.05), while ALETP co-treated groups showed enhanced percentage relaxation.</p><p><b>CONCLUSION</b>ALETP treatment of l-NAME-induced hypertensive rats promotes a relaxant effect on isolated cavernosa strips. ALETP shows potential in correcting erectile dysfunction in hypertension.</p>
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Objective To evaluate the efficacy of corpus cavernosum flushing combined with surgical shunt in the treatment of low-flow priapism(LFP).Methods We retrospectively reviewed 10 cases of LFP patients who were diagnosed and treated in our hospital from August 2010 to March 2017.The ages were from 28 to 67 years old,with average ages 44.8 years old,and the duration of erectile pain was 19 to 264 hours,with mean time 58.3 hours.Both doppler ultrasonography and analysis of blood gas indicated LFP.Comprehensive strategies were car-ried out to treat these patients.Results One case with chronic granulocytic leukemia(CGL) gave up treatment and died of acute transforma-tion three months later.Successful detumescence was achieved by combination of cavernosal flushing and different operation procedures for all of the other 9 cases.The follow-up duration ranged from 6 months to 12 months,which exhibited 3 cases with partial erectile dysfunction(ED) and 2 cases with complete ED respectively.Conclusion With the combination of cavernosal flushing and surgical shunt procedures,penis detumescence was successfully achieved.Treatment strategies should be carried out immediately as soon as LFP was diagnosed.
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Recent evidence shows that chronic ethanol consumption increases endothelin (ET)-1 induced sustained contraction of trabecular smooth muscle cells of the corpora cavernosa in corpus cavernosum of rats by a mechanism that involves increased expression of ETA and ETB receptors. Our goal was to evaluate the effects of alcohol and diabetes and their relationship to miRNA-155, miRNA-199 and endothelin receptors in the corpus cavernosum and blood of rats submitted to the experimental model of diabetes mellitus and chronic alcoholism. Forty-eight male Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D), and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study the protein expression of endothelin receptors by immunohistochemistry and expression of miRNAs-155 and -199 in serum and the cavernous tissue. Immunostaining for endothelin receptors was markedly higher in the A, D, and AD groups than in the C group. Moreover, a significant hypoexpression of the miRNA-199 in the corpus cavernosum tissue from the AD group was observed, compared to the C group. When analyzing the microRNA profile in blood, a significant hypoexpression of miRNA-155 in the AD group was observed compared to the C group. The miRNA-199 analysis demonstrated significant hypoexpression in D and AD groups compared to the C group. Our findings in corpus cavernosum showed downregulated miRNA-155 and miRNA-199 levels associated with upregulated protein expression and unaltered mRNA expression of ET receptors suggesting decreased ET receptor turnover, which can contribute to erectile dysfunction in diabetic rats exposed to high alcohol levels.
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Animals , Male , Rats , Alcoholism/metabolism , Diabetes Mellitus, Experimental/metabolism , Endothelin-1/analysis , MicroRNAs/analysis , Penis/metabolism , Receptor, Endothelin A/analysis , Receptor, Endothelin B/analysis , Alcoholism/complications , Alcoholism/physiopathology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/physiopathology , Immunohistochemistry , Penis/physiopathology , Rats, WistarABSTRACT
Objective@#To screen lentiviral vectors carrying siRNA which can specifically down-regulate the gene expression of the sphingosine-1-phosphate receptor 3 (S1PR3) in the corpus cavernosum smooth muscle (CCSM) cells of rats with spontaneous hypertension (SHT) and investigate the influence of the vectors on the signaling pathways of ROCK1, ROCK2 and eNOS in the CCSM cells of SHT rats.@*METHODS@#Using the S1PR3 mRNA sequence of the rat as an interfering target, we designed and synthesized three pairs of siRNA sequences (siRNA1, 2 and 3) targeting S1PR3 and one pair of negative control, and then constructed and packaged them into lentiviral vectors. We cultured the CCSM cells of SHT and Wistar-Kyoto (WKY) rats in vitro and randomly divided them into groups A (SHT untransfected control), B (SHT transfected and carrying negative control virus), C (SHT transfected and carrying siRNA1 targeting S1PR3), D (SHT transfected and carrying siRNA2 targeting S1PR3), E (SHT transfected and carrying siRNA3 targeting S1PR3), and F (WKY untransfected control). With the multiplicity of infection (MOI) = 60, we transfected the CCSM cells of the SHT rats with the lentiviral vector and then determined the expression of the green fluorescent protein (GFP) as well as the mRNA and protein expressions of S1PR3, ROCK1, ROCK2 and eNOS in the CCSM cells of the SHT and WKY rats by RT-PCR and Western blot.@*RESULTS@#Gene sequencing proved the successful construction of the lentiviral vector. The transfection efficiency of the CCSM cells of the rats was >80% in groups B, C, D and E. Compared with group A, the mRNA and protein expressions of S1PR3, ROCK1 and ROCK2 exhibited no significant difference in group B but were remarkably decreased in groups C, D, E and F (P0.05) but remarkably lower than those in group F (P0.05) but markedly increased in groups A, B, C and D (P< 0.05), while those of eNOS remarkably decreased in groups A, B, C, D and E (P< 0.05).@*CONCLUSIONS@#The three constructed lentiviral vectors carrying siRNA targeting different loci of the S1PR3 gene could significantly inhibit the expression of S1P3 as well as RhoA/Rho kinase signaling pathways in the CCSM cells of SHT rats, and the vector carrying siRNA3 exhibited the highest inhibitory effect.
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Animals , Male , Rats , Down-Regulation , Gene Expression , Genetic Vectors , Green Fluorescent Proteins , Metabolism , Lentivirus , Genetics , Myocytes, Smooth Muscle , Metabolism , Nitric Oxide Synthase Type III , Metabolism , Penis , Metabolism , RNA, Messenger , RNA, Small Interfering , Genetics , Metabolism , Random Allocation , Rats, Inbred WKY , Receptors, Lysosphingolipid , Genetics , Metabolism , Signal Transduction , Sphingosine-1-Phosphate Receptors , Transfection , rho-Associated Kinases , MetabolismABSTRACT
Objective@#To search for the methods of isolating, purifying and culturing corpus cavernosal endothelial cells (CCECs) from SD rats, observe their growth characteristics, and providing seed cells for the study of erectile dysfunction (ED).@*METHODS@#The corpus cavernosal tissue from the SD rat was digested with 0.1% elastase, followed by purification of CCECs with immunomagnetic beads. After further amplification, monoclonal CCECs were sorted out with the cloning cylinder and their morphological and proliferative characteristics were observed. The von Willebrand factor (VWF) in the CCECs was identified by immunofluorescence staining, the CD31 molecule detected by immumohistochemistry, the purity of the CCECs determined by flow cytometry, and the proliferation of the cells measured with CCK-8 and growth curves.@*RESULTS@#After 7 days of purification and culture, the CCECs were fused into a monolayer under the inverted phase-contrast microscope, arranged like flagstones. The growth curves showed that the CCECs were in latency with a low growth rate at 1－2 days, in the logarithmic growth phase with a rapid rate at 3－4 days, and into the platform phase around the 6th day. VWF was positively expressed in the CCECs with much green fluorescence, and so was CD31 with a large number of brownish particles. The positive rate of the CCECs which were labelled with the VWF purified with magnetic beads combined with cloning cylinders was up to (91.9±3.75)%.@*CONCLUSIONS@#High-purity rat CCECs can be cultured successfully using immunomagnetic beads combined with cloning cylinders, with stable proliferation and passage in the endothelial cell medium.
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Animals , Humans , Male , Rats , Cell Culture Techniques , Cell Movement , Cell Proliferation , Cells, Cultured , Endothelial Cells , Chemistry , Cell Biology , Physiology , Erectile Dysfunction , Pathology , Flow Cytometry , Immunomagnetic Separation , Penis , Cell Biology , Platelet Endothelial Cell Adhesion Molecule-1 , Rats, Sprague-Dawley , Sincalide , von Willebrand FactorABSTRACT
Ojective To investigate the direct effect of exogenous NOS inhibitor Nω-Nitro-L-arginine (L-NNA) on the erectile function of healthy male rats in order to clarify the mechanism of the erectile dysfunction of type 2 diabetic rats.Methods L-NNA (50 mg/kg) was administered by oral gavage to Sprague Dawley (SD) rats for 16 weeks to induce rat model of NOS inhibition.By the end of the experiment,corpora cavernosa was isolated from the rats under anesthetization and fixed in an organ chamber for the examination of relaxation function response to acetylcholine (ACh) to reflect erectile function.Enzymelinked immunosorbent assay (ELISA) was performed to determine the content of cyclic guanosine monophosphate (cGMP) in cavernosal tissue.NOS activity and nitric oxide (NO) content were measured by colorimetric method.Western blotting was employed to detect the protein expression of NOS and phosphodiesterase 5 (PDE5).The activity of the antioxidative enzyme superoxide dismutase (SOD) and content of the lipid peroxidative product malondialdehyde (MDA) were analyzed to reflect oxidative stress.Results In comparison with control group,the relaxation response to acetylcholine of corpus cavernosum was significantly impaired in L-NNA model rats,indicating penile erectile dysfunction.Either decreased contents of NO and cGMP or suppressed activity of NOS were observed in the corpus cavernosum of L-NNA model rats and in accompany with the down-regulation of endothelial NOS (eNOS) and neuronal NOS (nNOS) expression,up-regulation of inducible NOS (iNOS) and PDE5 expression as well as an increase of oxidative stress.Incubation of corpus cavernosum from control rats with L-NNA (1-10 μmol/L) ex vivo for 30 min could also inhibit the relaxation function responses to acetylcholine in a dose-dependent manner.Treatment with L-arginine ex vivo for 45 min could improve the impairments of relaxation function responses to acetylcholine of corpus cavernosum induced by L-NNA in vivo and ex vivo.Conclusions Exogenous NOS inhibitor L-NNA could induce penile erectile dysfunction in healthy male rats and the mechanism may be related to reducing NO content and increasing oxidative stress.
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AIM:To investigate the role of nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in erectile dysfunction of diabetic rats.METHODS:Type 2 diabetic rat model was established by 4 weeks of high-fat diet plus a single intraperitoneal injection of streptozotocin and continued high-fat diet feeding for 8 weeks.Corpus cavernosum was isolated from the rats under anesthetization,and the endothelium-dependent relaxation response to acetylcholine (ACh) was tested in an organ chamber to reflect erectile function.The level of ADMA in serum was detected.The NOS activity,nitric oxide (NO) content and cyclic guanosine monophosphate (cGMP) content in corpus cavernosum were measured.The protein expression of ADMA-NOS-NO pathway-related molecules and phosphodiesteras 5 (PDES) in the corpus cavernosum was detected by Western blot.Superoxide dismutase activity and malondialdehyde content were analyzed to evaluate oxidative stress.RESULTS:Elevated blood glucose and lowered insulin sensitivity were observed in the diabetic rats,indicating that type 2 diabetic rat model was successfully established.Compared with control group,the relaxation response to ACh of corpus cavernosum from diabetic rats was significantly decreased,which was accompanied with the elevation of serum ADMA level and reduction of NOS activity,NO content and cGMP content in the corpus cavernosum.The protein expression of ADMA-generating enzyme protein arginine methyltransferase 1 was up-regulated,while ADMA-metabolic enzymes dimethylarginine dimethylaminohydrolases 1 and 2,and ADMA-targeting enzymes endothelial NOS and neuronal NOS were down-regulated.The protein expression of PDE5 was up-regulated,accompanied with an increase in oxidative stress in the corpus cavemosum of diabetic rats.Incubation of isolated corpus cavernosum from normal rats with NOS inhibitor ADMA induced the similar relaxation dysfunction of corpus cavemosum response to ACh and decreased NO and cGMP contents in diabetic rats.CONCLUSION:Elevated endogenous NOS inhibitor ADMA plays an important role in erectile dysfunction of diabetic rats.The underlying mechanism may be related to the reduction of NO production and the increase in oxidative stress.
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AIM:To investigate the role of nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in erectile dysfunction of diabetic rats.METHODS:Type 2 diabetic rat model was established by 4 weeks of high-fat diet plus a single intraperitoneal injection of streptozotocin and continued high-fat diet feeding for 8 weeks.Corpus cavernosum was isolated from the rats under anesthetization,and the endothelium-dependent relaxation response to acetylcholine (ACh) was tested in an organ chamber to reflect erectile function.The level of ADMA in serum was detected.The NOS activity,nitric oxide (NO) content and cyclic guanosine monophosphate (cGMP) content in corpus cavernosum were measured.The protein expression of ADMA-NOS-NO pathway-related molecules and phosphodiesteras 5 (PDES) in the corpus cavernosum was detected by Western blot.Superoxide dismutase activity and malondialdehyde content were analyzed to evaluate oxidative stress.RESULTS:Elevated blood glucose and lowered insulin sensitivity were observed in the diabetic rats,indicating that type 2 diabetic rat model was successfully established.Compared with control group,the relaxation response to ACh of corpus cavernosum from diabetic rats was significantly decreased,which was accompanied with the elevation of serum ADMA level and reduction of NOS activity,NO content and cGMP content in the corpus cavernosum.The protein expression of ADMA-generating enzyme protein arginine methyltransferase 1 was up-regulated,while ADMA-metabolic enzymes dimethylarginine dimethylaminohydrolases 1 and 2,and ADMA-targeting enzymes endothelial NOS and neuronal NOS were down-regulated.The protein expression of PDE5 was up-regulated,accompanied with an increase in oxidative stress in the corpus cavemosum of diabetic rats.Incubation of isolated corpus cavernosum from normal rats with NOS inhibitor ADMA induced the similar relaxation dysfunction of corpus cavemosum response to ACh and decreased NO and cGMP contents in diabetic rats.CONCLUSION:Elevated endogenous NOS inhibitor ADMA plays an important role in erectile dysfunction of diabetic rats.The underlying mechanism may be related to the reduction of NO production and the increase in oxidative stress.
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The aim of this study was to investigate the effect and action mechanism of quercetin on penile corpus cavernosum smooth muscle (PCCSM). PCCSM precontracted with phenylephrine (Phe) was treated with four different concentrations of quercetin (10−7, 10−6, 10−5 and 10−4 M). PCCSM were preincubated with N-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) to block nitric oxide synthase and guanylate cyclase, respectively. The changes in PCCSM tension were recorded, and cyclic nucleotides in the perfusate were measured by radioimmunoassay. The interactions of quercetin with phosphodiesterase type 5 inhibitors (PDE5-Is) such as sildenafil, udenafil and mirodenafil, were also evaluated. PCCSM relaxation induced by quercetin occurred in a concentrationdependent manner. The application of quercetin to PCCSM pre-treated with L-NAME and ODQ significantly inhibited the relaxation. Quercetin significantly increased cGMP in the perfusate. Furthermore, quercetin enhanced PDE5-Is-induced relaxation of PCCSM. Quercetin relaxed the PCCSM by activating the NO-cGMP signaling pathway, and it may be a therapeutic candidate or an alternative treatment for patients with erectile dysfunction who do not completely respond to PDE5-Is.
Subject(s)
Humans , Male , Erectile Dysfunction , Guanylate Cyclase , Muscle, Smooth , NG-Nitroarginine Methyl Ester , Nitric Oxide Synthase , Nucleotides, Cyclic , Phenylephrine , Phosphodiesterase 5 Inhibitors , Quercetin , Radioimmunoassay , Relaxation , Sildenafil CitrateABSTRACT
Objective:To study the feasibility of transplantation of normal rat penile corpus cavernosum and major pelvic ganglion (MPG)into the renal subserous region of a Nu /Nu mouse based on allograft technology.Methods:Penile corpus cavernosum and MPG,harvested from Sprague-Dawley (SD)rats under sterile condition,were transplanted underneath the kidney capsule of Nu /Nu mice through the mi-crosurgery instruments and surgery microscope.The histopathologic changes and cellular proliferation in the transplanted penile corpus cavernosum and MPG were then analyzed at the end of 1week and 4 weeks after transplantation.Histological staining and immunohistochemical staining were used to evaluate the main outcome measures.Results:After 1 week,the tissue morphology of the transplanted corpus caverno-sum underneath the kidney capsule of Nu /Nu mice was consistent with normal penile corpus cavernosum, and blood could be observed in the penis cavernous sinus of the graft;after 4 weeks,the mophorlogy of the tranplanted corpus cavernosum near the kidney was consistent with normal penile corpus cavernosum, while fibrosis was noteworthy in the graft away from the kidney,but blood could still be seen in the penis cavernous sinus.After 1 week,the tissue morphology of the transplanted MPG was consistent with normal MPG,multiple islet-like cell clusters could be seen in the transplanted MPG in the renal subserous re-gion,and angiogenesis could be observed near the kidney;after 4 weeks,a network of blood vessels was clearly visible away from the kidney,and islet-like cell clusters were still clearly observed in the trans-planted MPG.In addition,ki67 positive cells were observed in the transplanted penile corpus cavernosum and MPG after 4 weeks of transplantation,which indicated that there was still cell proliferation activity in the grafts.Conclusion:The transplanted corpus cavernosum and MPG underneath the kidney capsule of Nu /Nu mice could survive at least 4 weeks.Moreover,the inner structure of the transplanted corpus ca-vernosum and MPG was close to the normal tissue.The underlining mechanism may be related to the lo-cal microenvironment underneath the kidney capsule of Nu /Nu mice and the neovascularization in the transplanted grafts.
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The present study aimed to examine the histological changes in the smooth muscles of corpus cavernosum and veins of rats as an eventual outcome of the ceaseless use of Sildenafil citrate. The comparison of the histological aftereffects of the veins among the control and experimental groups revealed extended thickness of tunica intima and media, as exhibited by a picture analyzer. The findings indicated that the steady usage of Sildenafil reduced smooth muscles and enabled the growth of collagen fibers in corpus cavernosum of penis and mass of veins.
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<p><b>Objective</b>To investigate the effect of salidroside on the expression of the connexin43 (Cx43) protein in the corpus cavernosum smooth muscle cells (CCSMCs) of hypoxic SD rats.</p><p><b>METHODS</b>CCSMCs were cultured in vitro and identified by immunofluorescence staining. The cells were divided into six groups: normal control (21% O2), hypoxia (1% O2), hypoxia+salidroside (HS) 8 μg/ml,HS 16 μg/ml, HS 32 μg/ml, and HS 64 μg/ml, and cultured for 48 hours. Then the relative expression of Cx43 in different groups was detected by Western blot.</p><p><b>RESULTS</b>The in vitro cultured CCSMCs grew well and 90% of the cells showed positivity for α-SMA and desmin on immunohistochemistry. Salidroside ≤64 μg/ml produced no obvious toxicity on the CCSMCs. The expressions of Cx43 and phosphorylated proteins were dramatically increased in the hypoxia group as compared with the normal control (P<0.01 and P<0.05). The HS groups all showed significantly higher expression of Cx43 than the hypoxia group (P<0.01), but the phosphorylation rate of the Cx43 proteins was remarkably decreased (P<0.01).</p><p><b>CONCLUSIONS</b>Hypoxia increases the expression of Cx43 in the CCSMCs of SD rats. Salidroside ≤64 μg/ml cannot reverse the hypoxia-induced change but can reduce the dephosphorylation of Cx43 in CCSMCs. It is deduced that salidroside can protect CCSMCs by decreasing the phosphorylation of Cx43 and suppressing hypoxia-induced formation of the gap junction channel.</p>
Subject(s)
Animals , Male , Rats , Actins , Metabolism , Cell Hypoxia , Cells, Cultured , Connexin 43 , Metabolism , Glucosides , Pharmacology , Myocytes, Smooth Muscle , Metabolism , Penis , Metabolism , Phenols , Pharmacology , Phosphorylation , Rats, Sprague-DawleyABSTRACT
Hypoxia is an independent risk factor of erectile dysfunction (ED), and the mechanisms of hypoxia causing ED are varied and complicated. Traditional studies related are concentrated on the changes of the corpus cavernosal endothelium and hormone levels in the body but have failed to achieve notable breakthroughs. Recent researches have demonstrated that such alterations in the corpus cavernosal microstructure as decreased corpus cavernosum smooth muscle cells of the contractile phenotype and fibrillation of the corpus cavernosum may be two important factors of hypoxia-induced ED. This review gives a brief introduction of the management of hypoxia-induced ED with the strategies of intervening in the corpus cavernosal microstructural changes, such as gene therapy, stem cell therapy, and induction of cell autophagy.
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The correlation between hypoxia and erectile dysfunction (ED) has been universally acknowledged for decades in the academic world. The phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) is regarded as one of the factors of hypoxia-induced ED, but the underlying mechanisms remain unclear. Recent researches show some correlation between autophagy and phenotypic modulation of CCSMCs, which may be associated with the overexpressions of PDGF, TGF-β, and vasoactive factors in the organism following hypoxia.
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Objective To validate the hypothesis that the phenotype reversion occurs in the smooth muscle cells in the corpus cavernosum of hypertensive rats with selenium food and explore selenium′s impact on erectile function. Methods 25 14-week-old male spontaneously hypertensive rates (SHR) were divided into 2 groups (SHR-ED-Se group n = 8 and SHR-ED-N group n = 9). SHR-ED-Se rats were fed with selenium diet, SHR-ED-N rats and WKY rats with normal diet. And 10 syngeneic normotensive rats (WKY) were used as control group. All rats were killed after 4-week feeding. Immunohistochemical staining and color image analysis system were used to observe expression of α-actin, desmin and osteopontin (OPN) in rats corpus cavernosum of different group. Results 2 SHR-ED-N rats died. Expression of α-actin of smooth muscle in corpus cavernosum in SHR-ED-N group was the lowest in all groups (P = 0.000), so did erection frequency (P 0.05). Conclusions Phenotype modulation of smooth muscle in corpus cavernosum of SHR rats can be reversed by selenium which means the smooth cells can transform from synthetic phenotype into the contractile phenotype, resulting ultimately in improving erectile function.
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Objective To investigate the modified method of intracavernous cannulation in monitoring intracavernous pressure (ICP) of rats.Methods The present study was conducted from October to December 2014.Twenty male Sprague-Dawley rats were randomly divided into 2 groups,the conventional group (cannulated in the crus of the penis) and the modified group (cannulated in the corporal body of the penis).The erectile function of the rats was assessed by measuring ICP/MAP (mean arterial pressure) ratio.The electrical-stimulation (ES) parameters were 5 V,15 Hz,5 ms,and 60 s for each stimulation.Results The differences in the basic ICP (14.9 ± 2.7 versus 15.5 ± 3.1 mmHg),ES-ICP (87.6 ± 7.5 versus 85.0 ± 6.2 mmHg),and ICP/MAP (71.3％ ± 6.6％ versus 72.5％ ± 6.3％) were not significant between the 2 groups (P ＞0.05 for all).Compared with the conventional group,the modified group could accurately cannulate the corpus cavernosum under direct vision,with an improved successful rate (100％ versus 80％),but there was no significant difference (P ＞ 0.05) in intracavernous pressure measurement.Conclusion The modified method of cannulating in the corpus cavernosum could have the advantage of higher successful rate,suggesting a feasible way for basic research of erectile dysfunction in rats.