The mechanistic study on Wa medicine Niang-Mu-Liang medicinal liquor mitigating diabetes mellitus erectile dysfunction in rats by inhibiting ferroptosis

Background:This study aims to investigate the therapeutic effect of Wa medicine Niang-Mu-Liang medicinal liquor(NML)on rats with diabetes mellitus erectile dysfunction(DMED)and its impact on the ferroptosis signaling pathway.Methods:Thirty Sprague-Dawley rats were randomly divided into three groups:Control,DMED,and NML.After establishing the DMED model,treatments were administered for 8 weeks.After the administration,apomorphine hydrochloride tests were conducted to measure the mass and organ index of testes and epididymides,sperm concentration and viability in each group.Penile corpus cavernosum tissues were stained with hematoxylin and eosin.Nitric oxide and cyclic guanosine monophosphate levels in the penile corpus cavernosum tissues were determined using biochemical kits and enzyme-linked immunosorbent assay,while the expression of proteins related to the ferroptosis signaling pathway was measured by Western blot.Results:Compared to the DMED group,the DMED rats treated with NML showed significantly increased erection frequency,testicular and epididymal mass and index,sperm count and viability,along with noticeable improvement in the pathological morphology of penile corpus cavernosum.The content of nitric oxide and cyclic guanosine monophosphate,and the expression of ferritin heavy chain,ferritin light chain,and glutathione peroxidase 4 proteins in penile corpus cavernosum tissue were elevated,while the expression of transferrin and STEAP3 proteins was reduced.Conclusion:NML can improve erectile function in DMED rats by inhibiting the ferroptosis signaling pathway.

Pathogenesis and treatment of diabetes mellitus-related erectile dysfunction: current therapies and potential challenges

Erectile dysfunction(ED)is one of the important complications of diabetes,which is very common in diabetic patients,affecting more than half of male patients,and the incidence of the disease is about 3.5 times that of the normal population.The pathogenesis of diabetic erectile dysfunction(DMED)is complex,involving nerve,vascular,endocrine,muscular and psychological aspects.At present,the therapeutic approaches of DMED include drug therapy,surgery,physical therapy and so on.This article provides a review of current research on the pathogenesis and treatment of DMED.Further elucidation of the pathogenesis of DMED and the development of new therapeutic approaches are of great significance for the prevention and treatment of DMED.

Mechanism of the Xuefu Zhuyu decoction in treating diabetes mellitus erectile dysfunction based on the CaSR/Gq-PLC-PKC pathway

Background:To investigate the mechanism of Xuefu Zhuyu decoction in the treatment of diabetes mellitus erectile dysfunction.Methods:Rats with diabetes mellitus erectile dysfunction were developed using streptozocin and randomly assigned into model,low-dose herbal,and high-dose herbal groups.All rats were administered normal saline or the corresponding drugs by oral gavage for 4 weeks.The related indices were detected using enzyme-linked immunosorbent assays,immunohistochemistry,western blotting,and transmission electron microscopy.Results:The levels of lectin-like oxidized low-density protein receptor-1,endothelin-1,NADH oxidase,vascular cell adhesion molecule-1,and intercellular adhesion molecule-1 in the model group were significantly higher than they were in the mock group but lower than they were in the herbal treatment group.The level of nitric oxide was lower in the model group than was in the mock group but higher than the level in the herbal treatment group.The calcium-sensitive receptor,phospho-protein kinase Cδ/protein kinase Cδ,phosphorylated c-Jun amino-terminal kinase/c-Jun amino-terminal kinase,and phospho-P38 mitogen-activated protein kinase/P38 mitogen-activated protein kinase expression levels in the model group were higher than were in the mock group but lower than were in the herbal treatment group.The structures of the Corpus cavernosum penis endothelial cells were significantly improved in the herbal treatment group than they did in the model group.Conclusion:Xuefu Zhuyu decoction can decrease injury to the endothelium,improve vascular endothelial diastolic and contractive function,and inhibit vascular fibrosis in rats with diabetes mellitus erectile dysfunction.This mechanism may be related to the CaSR/Gq-PLC-PKC pathway.

Erectile dysfunction as a predictor of asymptomatic coronary artery disease in elderly men with type 2 diabetes

1 Introduction Erectile dysfunction （ED） and coronary artery disease （CAD） are closely linked, as both conditions share the same cardiovascular risk factors. Indeed, these risk factors can determine endothelial dysfunction that represents the common underlying mechanism of both ED and CAD. The prevalence of ED is about three-fold higher among diabetic patients than in the general population and a higher prevalence of CAD has been observed in people with diabetes when compared to non-diabetic subjects.Some studies showed that ED can be a powerful marker of silent CAD and a strong predictor of cardiovascular events in apparently uncomplicated type 2 diabetic patients Therefore ED is now considered as a sentinel symptom of silent CAD, as ED often precedes the onset of myocardial ischemia itself by many years.

Neurovascular Evaluation in Eugonadal Men with Type 2 Diabetes Mellitus and Erectile Disfunction:A Comparative Study between Responders and Not Responders to Phosphodiesterase 5 Inhibitors

The aim of our study was to evaluate functional alterations of the corpus cavernusum and its correlation with the lack of response to treatment with PDE5i in eugonadal patients with Type 2 Diabetes Mellitus and Erectile Dysfunction. In this prospective randomized study we included 157 patients. All were treated with 5 mg tadalafil daily and 100 mg sildenafil on demand and the response to treatment was assessed in 6 month by dividing them into 2 groups: G1: Good response. Significative improvement of erectile function according to IIEF-5, and G2: There was not an improvement with the treatment. At the end of the treatment we performed neurological and vascular studies to both groups. Also we performed CC-EMG in order to evaluate penile autonomic neuropathy. 82 patients were included in G1 and 75 in G2. The time evolution of the ED was 1.5 years for G1 and 5 years for G2. Average fasting glucose and glycosilated hemoglobin values were significantly higher in G2 than in G1. Also we observed significant differences in penile vascular parameters between both groups. Peripheral neuropathy parameters did not show differences between both groups. Cavernous smooth muscle electromyography showed asynchronous and asymetric potentials in G1 (minimal autonomic neuropathy) and denervation potentials in G2 characteristic of severe CC damage. It is concluded that vascular and autonomic alterations are causes of severe CC damage and lack of response to treatment with PDE5i in this population. Peripheral neuropathy is not part of this process.

Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, roTOR and the NO-cGMP pathway

Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.

Prevalence, correlates, attitude and treatment seeking of erectile dysfunction among type 2 diabetic Chinese men attending primary care outpatient clinics

To investigate the prevalence, correlates, attitude and treatment seeking behavior of erectile dysfunction （ED） in type 2 diabetes mellitus （T2DM） patients in the primary care setting, a multi-center cross-sectional survey using a structured anonymous self-administered questionnaire was performed in 10 general outpatient clinics. Of the 603 subjects （91% response rate）, the prevalence of ED men, as defined by the International Index of Erectile Function, was 79.1%. Most subjects had mild ED （28.9%）, followed by mild-to-moderate ED （27.9%）, then moderate ED （13.4%） and severe ED （9%）. Nearly 55% of those with ED did not consider themselves as having ED. Less than 10% of them had ever sought medical treatment, although 76.1% of them wished to receive management from doctor（s） should they be diagnosed with ED. They considered the most important management from doctors to be clinical assessment （41.7%）, followed by management of potential underlying cause （37.8%）, referral to specialist （27.5%）, education （23.9%）, prescription of phosphodiesterase type 5 inhibitors （16.9%） and referral to ~：ounseling service （6.7%）. The prevalence of ED was strongly associated with subjects who thought they had ED （odds ratio （OR） = 90.49 （20.00-409.48, P 〈 0.001）） and were from the older age group （OR = 1.043 （1.011-1.076, P = 0.008））. In conclusion, ED is highly prevalent among T2DM men. The majority of them wanted management from doctors should they have ED, but only a minority would actually voice out the request. Screening of ED among T2DM men using structural questionnaire allowed the diagnosis of more than half of the ED cases, which otherwise would have gone undiagnosed.

Stem cell therapy and diabetic erectile dysfunction:A critical review

Erectile dysfunction(ED)has been identified as one of the most frequent chronic complications of diabetes mellitus(DM).The prevalence of ED is estimated to be about 67.4%in all DM cases worldwide.The pathophysiological process leading to ED involves endothelial,neurological,hormonal,and psychological factors.In DM,endothelial and neurological factors play a crucial role.Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM.The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery.However,these treatments are limited in terms of just relieving the symptoms,but not resolving the cause of the problem.The use of stem cells for treating ED is currently being studied mostly in experimental animals.The stem cells used are derived from adipose tissue,bone,or human urine.Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue.However,research on stem cell therapy for ED in humans remains to be limited.Nevertheless,significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.

Relationship between Gut Microbiota and Type 2 Diabetic Erectile Dysfunction in Sprague-Dawley Rats

In order to investigate the relationship between gut microbiota and type 2 diabetic erectile dysfunction（T2DED）, we analyzed the characteristics of gut microbiota in the Sprague-Dawley（SD） rats with T2DED. Thirty-five SD rats were randomly divided into two groups： control group（n=15） with normal diet, and experimental group（n=20） with construction of T2D model. Faecal and serum samples were collected at 2nd and 8th week after establishment of T2D model, respectively. Faecal samples were used for analysis of gut microbiota, and serum samples for detection of trimethylamine N-oxide（TMAO）, lipopolysaccharide（LPS）, and inflammatory factors like interleukin-1（IL-1）, IL-2, IL-10, and monocyte chemoattractantprotein-1（MCP-1）. The main compositions of gut microbiota were Bacteroidetes, Proteobacteria and Firmicutes at the phylum level, and Oscillospira, Allobaculum, Bacteroides, Ruminococcus, SMB53, Prevotella, Coprococcus, Sutterella and Blautia at the genus level with relatively higher abundance in all SD rats. The relative abundance of Enterococcus, Corynebacterium, Aerococcus, Facklamia（opportunistic pathogens in most case） increased, and that of Allobaculum, Bifidobacterium, Eubacterium, Anaerotruncus（beneficial bacteria） decreased in T2DED group as compared with that at 2nd week after establishment of T2D model（T2D2 group）. The serum contents of TMAO, LPS, IL-1, IL-2, IL-10 and MCP-1 in T2DED group were significantly higher than those in control group. The gut microbiota of T2DED rats was inhibited. The gut microbiota of T2DED rats had changed, as the relative abundance of beneficial bacterium was decreased while that of opportunistic pathogens was increased. The variations of gut microbiota might lead to inflammation and prompt the emergence of erectile dysfunction in the rats with T2D. TMAO might play an important role in the formation of T2DED.

Long-term treatment with intracavernosal injections in diabetic men with erectile dysfunction

Aim： To assess the behavior of patients with diabetes mellitus （DM） and erectile dysfunction （ED） during 10 consecutive years of treatment with self-injection of vasoactive drugs. Methods： Thirty-eight diabetic men, including 12 with type Ⅰ and 26 with type Ⅱ diabetes, were followed up regularly for 10 years after they began self-injecting for severe ED. Real time rigidity assessment was used for the objective determination of the initial dosage and then doses were regulated in order to introduce an erection suitable for penetration and maintenance of erection for approximately 30 min. Patients were followed up every two months, and doses were increased only when the treatment response was not satisfactory. Results： The number of injections used per year by the patients was reduced each year （mean numbers： 50 in the first year and 22.5 in the 10th） and treatment shifted towards stronger therapeutic modalities （mixtures of vasoactive drugs instead of prostaglandin E1 alone）. Type Ⅰ diabetic men were standardized to a level of treatment as early as 5 years after the initiation of treatment. That level was finally reached by type Ⅱ patients after another 4-5 years. Conclusion： Treatment with self-injections of vasoactive drugs in diabetic men with severe El） is a safe and effective alternative in the long term. Diabetic men of both types show the same preferences in quality and quantity of treatment after 10 years. The key point for maintenance in treatment is the adjustment of the therapeutic method and dosage to optimal levels for satisfactory erections. （Asian J Androl 2006 Mar; 8： 219-224）

Magnitude and Factors Contributing to Erectile Dysfunction among Diabetic Men Attending the Diabetic Clinic at Debre Tabor Comprehensive and Specialized, Hospital in North West, Ethiopia 2020, Institutional Based Cross-Sectional Study

Background: Erectile dysfunction, which is defined as difficult to attain and maintain an erectile function enough to permit sufficient sexual performance, is accepted to be a big problem especially among diabetic patients. Objective To assess the Magnitude and factors contributing to Erectile Dysfunction Among Diabetic men attending the diabetic clinic in Debre Tabor Comprehensive and Specialized hospital, North West Ethiopia. Methods: Hospital based cross-sectional study was conducted on 362 participants in Debre Tabor Comprehensive and Specialized Hospital from August - December 2020 using systematic random sampling technique. Data were analyzed with SPSS Version 23. Binary and multivariable logistic regressions were done to identify factors which were contributing to erectile dysfunction. P-value < 0.05 and the corresponding 95% CI of odds ratios were considered to declare the result as statistically significant. Results: Three hundred sixty-two diabetes patients participating in the study with the mean age being 44.4 ± 14.47 (range: 18 - 78) years were interviewed. The majority (59.7% with CI: 54.4:64.6) of the diabetes patients suffered from erectile dysfunction and 13.3% (95% CI 17.8% - 26.8%) were found to have severe erectile dysfunction. Bi-variable analysis showed duration of diabetes (>10 years), type of diabetes (type II), physical exercise, drinking alcohol, BMI, blood glucose, and blood pressure were associated with erectile dysfunction at 5% level (p ≤ 0.05). Multiple logistic regression analysis revealed that duration of diabetes 10 years (AOR = 6.2, 95% CI: 2.78 - 13.85, p = 0.001), co-existing hypertension (AOR: 3.59, 95% CI: 1.58 - 8.19, p = 0.002), physically inactive (AOR = 2.87, 95% CI: 1.53 - 8.31, p = 0.003), unsafe level alcohol intake (AOR: 3.09;95% CI 1.45 - 6.59*, p = 0.003) and raised blood glucose (AOR: 15.26, 95% CI: 7.82 - 29.77, p = 0.004) were independent risk factors but no association was found with other variables. Conclusion: The magnitude of erectile dysfunction in this study population was 59.7% and associated with the type of diabetes;duration of diabetic, physical exercise, alcohol drinking, increase in blood pressure, and elevated blood glucose level were independently correlated with erectile dysfunction.

STUDY ON HEMODYNAMICS OF ERECTION IN DIABETIC ERECTILE DYSFUNCTION

Objective To study the cavernosa hemodynamics in diabetic erectile dysfunction ( ED).Methods 22 diabetic and 35 psychic ED patients were studied by intracavernosum injection of a mixture papaver-ine and phentolamine (30/1mg) to assess the hemodynamics changes of the corpus cavernosum by means of colour duplex ultrasonography. Results The average hemodynamics data of the diabetic ED patients vs that of the psy-chogenic ED patients in terms of peak flow velocity (PFV):20. 06±7.15cm/s vs 35. 82±9. 41cm/s, end diastolic velocity (EDV) : 8. 82±0. 35cm/s vs 5. 51±0. 42cm/s,artery diameter (Ad) : 0. 78±0. 25cm vs 1. 01±0. 42cm, vein diameter ( Vd) : 1.05±0. 32mm vs 1.21±0. 45mm, resistance index(RI) : 0. 72±0. 28 vs 0. 98±0. 31,mean velocity of artery (MV):6. 71±0. 27cm/s vs 10. 31±3. 32cm/s, dorsal deep vein flow(DDVF) : 28. 81±6. 32cm/ s vs 25. 74±0. 58cm/s. Stasticstical differences existed in PFV, Ad,RI and MV(P <0. 01). The arterial wall is thick and rigid in diabetic ED patients. Conclusion Atheroscleorsis and veno-occlusive dysfunction of the corpus cavernosum are essential to the development of diabetic ED.

Peyronie's disease:a silent consequence of diabetes mellitus

Aim： To investigate the clinical characteristics of patients with Peyronie＇s disease （PD） and diabetes mellitus （DM）. Methods： During an 8-year period, a total of 307 men seen at our outpatient clinic were diagnosed with PD. Clinical characteristics, penile deformities and the erectile status of patients with PD and DM together （n = 102） were retrospectively analyzed and compared to patients with PD alone with no risk factors for systemic vascular diseases （n = 97）. Results：The prevalence of PD among men with DM and sexual dysfunction was 10.7 %. The mean age of diabetic patients with PD was （55.9 ± 8.9） years; in the no risk factor group it was （48.5 ± 9.0） years （P 〈 0.05）. The median duration of DM was 5 years. The majority of diabetic patients with PD （56.0 %） presented in the chronic phase （P 〈 0.05）, and they were more likely to have a severe penile deformity （〉 60°） than the no risk factor group （P 〈 0.05）. In the diabetic group, the most common presenting symptom was penile curvature （81.4%）, followed by a palpable nodule on the shaft of the penis （22.5%） and penile pain with erection （14.7%）. A total of 19.6% of patients were not aware of their penile deformities in the diabetic group. Erectile function, provided by history and in response to intracavernosal injection and a stimulation test, was significantly diminished in patients with PD and DM （P 〈 0.05）. Conclusion： DM probably exaggerates the fibrotic process in PD. Diabetic patients with PD have a higher risk of severe deformity and erectile dysfunction （ED）. PD seems to be a silent consequence of DM and should be actively sought in diabetic men. （Asian JAndrol 2006 Jan; 8： 75-79）

Erectile dysfunction in chronic kidney disease:From pathophysiology to management

Chronic kidney disease(CKD) is encountered in millions of people worldwide,with continuously rising incidence during the past decades,affecting their quality of life despite the increase of life expectancy in these patients.Disturbance of sexual function is common among men with CKD,as both conditions share common pathophysiological causes,such as vascular or hormonal abnormalities and are both affected by similar coexisting comorbid conditions such as cardiovascular disease,hypertension and diabetes mellitus.The estimated prevalence of erectile dysfunction reaches 70% in end stage renal disease patients.Nevertheless,sexual dysfunction remains under-recognized and under-treated in a high proportion of these patients,a fact which should raise awareness among clinicians.A multifactorial approach in management and treatment is undoubtedly required in order to improve patients' quality of life and cardiovascular outcomes.

Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats

The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabetic erectile dysfunction （ED）. A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure （ICP） monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation （P〈O.01 for both comparisons）. Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.

Efficacy and safety of low-intensity shockwave therapy plus tadalafil 5 mg once daily in men with type 2 diabetes mellitus and erectile dysfunction:a matched-pair comparison study

Low-intensity extracorporeal shockwave therapy(LiESWT)represents a promising treatment for patients with erectile dysfunction(ED).We investigated the efficacy of LiESWT combined with tadalafil 5 mg once daily in men with type 2 diabetes mellitus(T2DM)and ED and compared LiESWT protocols administering different number of shockwaves.We performed a retrospective matched-pair comparison using data from a prospectively maintained database.Seventy-eight patients who received tadalafil 5 mg once dai7ly for 12 weeks+LiESWT performed with an electrohydraulic source for 3 weeks(Group A)were matched 1:1 to patients who received tadalafil 5 mg once daily alone for 12 weeks(Group B).A subgroup analysis was performed according to the number of shockwaves delivered during each session(1500,1800,and 2400 in subgroup A1,A2,and A3,respectively).The mean International Index of Erectile Function-5(IIEF-5)score variations with respect to baseline recorded at 4,12,and 24 weeks after the end of the treatment were investigated as treatment outcomes.The mean IIEF-5 scores significantly improved in all groups and subgroups at 4-week follow-up without intergroup differences.At 12-and 24-week follow-up,the mean IIEF-5 improvement was significantly higher among patients in the A3 subgroup(+5.0±2.1[P<0.001]and+4.7±2.3[P<0.001],respectively).The combined approach with tadalafil 5 mg once daily and LiESWT with a protocol involving 2400 shockwaves provides significant advantages in terms of IIEF-5 improvement and durability compared to tadalafil 5 mg once daily alone in patients with T2DM and ED.

Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction(DMED)a challenging endeavor.Notable factors contributing to DMED include oxidative stress,nitric oxide(NO)/cyclic guanosine monophosphate(cGMP)pathway activation,and apoptosis,while nitro-oleic acid(NO,-OA)has been shown to be beneficial in treating these aspects of this condition.We,herein,investigated the effects and possible mechanisms of NO,-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes.Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group.However,in response to 4 weeks of NO,-OA treatment,there was an improvement in erectile function.The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group.The expression of proapoptotic factors was increased,while that of antiapoptotic factors was decreased in the DMED group.Moreover,the cell morphology in the cavernous tissue of the DMED group also changed adversely.NO,-OA treatment significantly reversed all these changes observed in the DMED group.In conclusion,NO,-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress,activation of the NO/cGMP pathway,and a reduction in apoptosis.

伊木萨克片联合NLRP3炎症小体抑制剂MCC950通过抑制氧化应激改善DMED大鼠勃起功能的研究

目的探讨伊木萨克片联合核苷酸结合寡聚结构域样受体蛋白3(NLRP3)炎症小体抑制剂MCC950是否可通过抑制阴茎组织中氧化应激水平改善糖尿病性勃起功能障碍(DMED)大鼠的勃起功能。方法选取32只正常雄性SD大鼠构建糖尿病大鼠模型,造模第2、4、6、8周后通过阿扑吗啡(APO)和交配实验筛选出24只DMED大鼠。连续药物干预2周后,采用免疫荧光法检测大鼠阴茎组织中NLRP3蛋白表达,采用试剂盒法检测阴茎组织中活性氧(ROS)和丙二醛(MDA)表达水平,采用Western blot法检测阴茎组织中超氧化物歧化酶(SOD)-1、还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX)1、NOX2蛋白表达。结果DMED组阴茎组织中NLRP3蛋白表达高于N组、MCC950组、Y组、MCC950+Y组,MCC950+Y组阴茎组织中NLRP3蛋白表达低于MCC950组、Y组(P<0.05)。DMED组阴茎组织中ROS和MDA表达水平高于N组、MCC950组、Y组、MCC950+Y组,MCC950+Y组阴茎组织中ROS和MDA表达水平低于MCC950组、Y组(P<0.05)。DMED组阴茎组织中NOX1和NOX2蛋白表达高于N组、MCC950组、Y组、MCC950+Y组,SOD-1蛋白表达低于N组、MCC950组、Y组、MCC950+Y组;MCC950+Y组阴茎组织中NOX1和NOX2蛋白表达低于MCC950组、Y组,SOD-1蛋白表达高于MCC950组、Y组(P<0.05)。结论伊木萨克片和MCC950均可通过抑制阴茎组织中氧化应激水平改善DMED大鼠的勃起功能,且两者联合干预效果更佳。

Lipoxin A4 improves erectile dysfunction in rats with type I diabetes by inhibiting oxidative stress and corporal fibrosis

Previous studies have shown that oxidative stress and corporal fibrosis in penile tissues of rats were key pathological factors of erectile dysfunction induced by diabetic mellitus （DMED）. Lipoxin A4 （LXA4） was reported to inhibit oxidative stress and fibrosis diseases, while whether it could exert a protective role on erectile function was not clear. Type I diabetic mellitus （DM） was induced in thirty male lO-week-old Sprague-Dawley rats using streptozotocin. Ten weeks later, twenty-two rats with DMED confirmed by an apomorphine test were divided into two groups： the DMED group （n = 11） and the DMED ＋ LXA4 group （n = 11; LXA4 injection daily for 4 weeks）. In addition, another ten age-matched rats formed the Control group. We found that erectile function was significantly impaired in the DMED group compared with the Control group, but was improved in the DMED ＋ LXA4 group. Similarly, the over-activated oxidative stress and impaired endothelial function in the DMED group were both improved in the DMED ＋ LXA4 group. Moreover, the DMED group showed serious corporal fibrosis, which was also inhibited by the treatment of LXA4 in the DMED ＋ LXA4 group. Taken together, LXA4 could exert an inhibition role on oxidative stress and fibrosis to improve DMED effectively.

G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes

Type 2 diabetes mellitus (T2DM)is a common cause of erectile dysfunction (ED).It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2)overexpression contributes to diabetic endothelial dysfunction and oxidative stress,which also underlies ED in T2DM.We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM.T2DM rats were established by feeding with a high-fat diet (HFD)for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ),followed by continuous feeding with a HFD for 6 weeks.GRK2 was inhibited by IP injection of paroxetine,a selective GRK2 inhibitor,after STZ injection.Insulin challenge tests,intracavernous pressure (ICP), GRK2 expression,the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS)pathway,nicotinamide adenine dinucleotide phosphate (NADPH)oxidase subunit gp91phox,nitric oxide (NO),reactive oxygen species (ROS)production,and apoptosis in cavernosal tissue were examined.Less response to insulin injection was observed in T2DM rats 2 weeks after HFD.Markedly increased GRK2 expression,along with impaired Akt/eNOS pathway,reduced NO production,increased gp91phox expression and ROS generation,increased apoptosis and impaired erectile function were found in T2DM rats.inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling,restored NO production,downregulated NADPH oxidase,subsequently inhibited ROS generation and apoptosis,and ultimately preserved erectile function.These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED,and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.