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<0.01 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.     

褪黑素抗氧化治疗糖尿病大鼠阴茎勃起功能障碍的研究

目的 观察褪黑素对糖尿病大鼠阴茎勃起功能的影响,探讨氧化应激在糖尿病性勃起功能障碍发病机制中的作用.方法 一次性腹腔注射STZ建立糖尿病大鼠模型,随机分为糖尿病组、褪黑素(MT)治疗组以及对照组.8周后通过电刺激各组大鼠勃起神经来检测海绵体内压,评价勃起功能;采用硫代芭比妥酸法检测阴茎海绵体组织中丙二醛(MDA)含量,黄嘌呤氧化酶法测超氧化物氧化酶(SOD)活性;免疫组化染色半定量分析各组大鼠阴茎海绵体中平滑肌及内皮的含量.结果 与正常对照组相比,阴茎海绵体组织中MDA含量显著增加(P＜0.01),SOD活性降低(P＜0.05),最大海绵体内压(ICP)亦显著降低(P＜0.05);与糖尿病组相比,MT组大鼠海绵体MDA含量明显降低(P＜0.05),其SOD活性和ICP显著升高(P＜0.05);且其海绵体平滑肌及海绵窦内皮细胞含量明显提高.结论 MT可通过改善组织中氧化应激水平,促进阴茎海绵体平滑肌和内皮组织修复,提高勃起功能;抗氧化治疗可能为糖尿病性勃起功能障碍的防治提供新的策略.     

还原型谷胱甘肽在预防糖尿病大鼠勃起功能障碍中的研究

目的探讨还原型谷胱甘肽(GSH)在预防糖尿病大鼠勃起功能障碍中的作用。方法通过腹腔注射链脲佐菌素65mg/kg建立糖尿病大鼠模型,然后随机分成DM组和DM+GSH组,DM+GSH组每天肌肉注射GSH200mg/kg。10周后观察大鼠勃起功能,并获取海绵体组织检测其谷胱甘肽、一氧化氮合酶(NOS)与丙二醛(MDA)水平,用TUNEL法检测细胞凋亡。结果成功建立糖尿病大鼠模型。与未注射GSH的DM组相比,DM+GSH组和正常对照组(C组)勃起功能更好,勃起率分别是20%,62.5%和100%。GSH水平DM+GSH组和C组明显比DM组高,其3组含量每克蛋白分别是(75.83±15.62)、(61.47±8.65)和(35.03±12.29)mg(P<0.05);NOS水平在DM+GSH组每毫克蛋白为(133.9±31.9)U,与正常对照组每毫克蛋白为(142.2±31.2)U相当,但较DM组每毫克蛋白为(58.4±18.9)U高(P<0.05);MDA含量在DM组每毫克蛋白为(3.71±0.62)nmol,明显高于正常对照组和DM+GSH组(P<0.05),这两组每毫克蛋白为(2.08±0.34)nmol和(2.44±0.28)nmol;细胞凋亡率在DM组、DM+GSH组和C组的分别是(22.6±3.6)%、(10.8±1.7)%和(7.2±2.1)%(P<0.05)。结论还原型谷胱甘肽对糖尿病大鼠阴茎组织有较好的抗氧化作用,能减少细胞凋亡,对延缓糖尿病性ED的发生有一定的作用。     

The effects of long-term administration of tadalafil on STZ-induced diabetic rats with erectile dysfunction via a local antioxidative mechanism

Type 5 phosphodiesterase inhibitors (PDE5Is) are well known being effective via the nitric oxide and cyclic guanosine monophosphate (NO–cGMP) pathway and are widely used in the treatment of diabetic erectile dysfunction (ED). However, it is unclear whether other pathways may be involved in the treatment of diabetic ED with PDE5Is. The purpose of this study was to clarify the role of antioxidants in diabetic ED treatment through the long-term administration of PDE5Is. Three groups of Sprague–Dawley rats were utilized: Group N, the normal control; Group D, streptozotocin (STZ)-induced diabetic rats as a control; and Group D+T, STZ-induced diabetic rats who received oral administration of tadalafil for 8 weeks. Erectile function was assessed by intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrical stimulation of the cavernous nerve before euthanasia. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) of cavernous tissue were assessed by biochemical analysis. The morphology of mitochondria was observed by electron microscopy. The ICP/MAP ratio was higher in Group D+T than in Group D (P<0.05). The levels of MDA decreased and the activities of SOD increased in Group D+T in comparison with Group D (P<0.05). The mitochondrial membrane potential level of cavernous tissue in diabetic rats was partially recovered by tadalafil treatment for 8 weeks. The morphology changes of mitochondria were also remarkably ameliorated in Group D+T. Collectively, the long-term administration of tadalafil in diabetic rats partially reduced oxidative stress lesions of the penis via a local antioxidative stress pathway. Long-term dosages of tadalafil given once daily beginning soon after the onset of diabetes may aid in preventing rats from developing diabetic ED.     

Assessment of erectile dysfunction in diabetic patients

Erectile dysfunction (ED) aetiology is multifactorial, including endocrine, neurological, vascular, systemic disease, local penile disorders, nutrition, psychogenic factors, and drug-related. This study was performed to compare the relevant comprehensive biochemical parameters as well as the clinical characteristics in diabetic ED and healthy control subjects and to assess the occurrence of penile neuropathy in diabetic patients and thus the relationship between ED and diabetes. A total of 56 patients accepted to undergo assessment for penile vasculature using intracavernosal injection and colour Doppler ultrasonography. Of the 56 diabetic patients, 38 patients were found with normal blood flow and thus they were considered as the diabetic-ED group, whereas, ED diabetic patients with an arteriogenic component were excluded. These patients with an age range between 17 and 58 years, complaining of ED, with duration of diabetic illness ranging from 2 to 15 years. The Control group comprised of 30 healthy subject aged between 19 and 55 years. Peripheral venous levels of testosterone, prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), malondialdehyde and glycosylated haemoglobin (HbA(1)c) were obtained in all subjects. Valsalva manoeuvre and neurophysiological tests were also determined. Testosterone, prolactine, FSH, LH, and TSH hormones of the diabetic patients were not significantly different from those of the control group. Diabetic patients with ED have higher HbA(1)c and oxidative stress levels while the R-R ratio was significantly decreased. Bulbocavernosus reflex latency was significantly prolonged, whereas its amplitude, the conduction velocity and amplitude of dorsal nerve of penis were significantly reduced in the diabetic patients. We concluded that although ED is a multifactorial disorder, yet, the present study revealed that in ED patients without arteriogenic ED a neurogenic component is present. Furthermore, the complex effect of the Valsalva manoeuvre on cardiovascular function is the basis of its usefulness as a measure of autonomic function. Thus, it can be of value in the diagnosis of ED although these hypotheses require follow-up in a large study cohort.     

糖尿病大鼠阴茎海绵体细胞凋亡的实验研究

目的 观察糖尿病(DM)大鼠阴茎海绵体细胞凋亡,探讨DM性阴茎勃起功能障碍(ED)的发病机理。方法 本文通过四氧嘧啶(Alloxan,AXN)诱导的DM大鼠模型,饲养8周后处死动物并取阴茎海绵体。用琼脂糖凝胶电泳法进行DNA片段分析;用TUNEL法检测细胞凋亡。结果 DM组DNA片段分析出现凋亡特征性梯带。DM组较对照组勃起组织凋亡细胞数明显增多(P<0.01)。结论 DM大鼠阴茎海绵体凋亡细胞增加,细胞凋亡可能是DM性ED的发病机理。     

胰岛素对糖尿病大鼠阴茎内nNOS神经纤维的影响

目的探讨糖尿病性阴茎勃起功能障碍（ED）的发病机制及胰岛素的治疗作用。方法注射链脲佐菌素建立糖尿病（DM）大鼠模型，胰岛素治疗组于成模后注射胰岛素。7周和12周后注射阿扑吗啡（APO）进行大鼠阴茎勃起功能实验，取大鼠阴茎和血浆，用ABC免疫组织化学法观察nNOS神经纤维的变化。测定血浆NOS活性。结果（1）与对照组相比，DM组大鼠阴茎勃起次数明显减少;胰岛素治疗后症状缓解;（2）与对照组相比，DM组血浆NOS活性明显增高;DM组血浆NOS活性与病程延长呈负相关;与DM组比较，胰岛素治疗组血浆NOS活性明显降低;（3）与对照组相比，DM组阴茎内nNOS阳性神经纤维明显减少;与DM组比较，胰岛素治疗组nNOS阳性神经纤维表达增加。结论糖尿病性ED阴茎内nNOS阳性纤维的数量及光密度随DM病程的延长而下降;早期给予胰岛素治疗可预防糖尿病大鼠ED的出现及阴茎内nNOS含量的下降。     

Evaluation of daily avanafil efficacy in improving the endothelial function in Egyptian males with erectile dysfunction

Avanafil is a highly selective and potent oral phosphodiesterase type 5 inhibitor. However, its impact on the soluble markers of endothelial function has not been investigated yet. This study was conducted to assess the effect of daily avanafil on the endothelial markers' serum level and erectile function in patients with erectile dysfunction. In this work, we randomly divided 140 males with erectile dysfunction and other diseases commonly associated with endothelial dysfunction like diabetes mellitus, hypertension and dyslipidaemia into two equal groups: treatment group, treated with 50mg daily oral avanafil, and control group, treated with placebo. The International Index of Erectile Function-5 score and the serum levels of nitric oxide, cyclic guanosine monophosphate and endothelin-1 as markers of endothelial function were measured at baseline and after four weeks of treatment in both groups. At the end of treatment period, those randomised to avanafil achieved statistically significant improvement in erectile function, nitric oxide, cyclic guanosine monophosphate and endothelin-1 levels from baseline versus placebo regardless the type and duration of associated comorbidity as well as the duration and severity of erectile dysfunction. These results permitted us to suggest that daily avanafil can improve the impaired endothelial function associated with the erectile dysfunction.     

Vascular dysfunction in diabetes: The endothelial progenitor cells as new therapeutic strategy

The vascular endothelium is a critical determinant of dia- betes-associated vascular complications, and improving endothelial function is an important target for therapy. Diabetes mellitus contributes to endothelial cell injury and dysfunction. Endothelial progenitor cells (EPCs) play a critical role in maintaining endothelial function and might affect the progression of vascular disease. EPCs are essential to blood vessel formation, can differentiate into mature endothelial cells, and promote the repair of damaged endothelium. In diabetes, the circulating EPC count is low and their functionality is impaired. The me- chanisms that underlie this reduced count and impaired functionality are poorly understood. Knowledge of the status of EPCs is critical for assessing the health of the vascular system, and interventions that increase the number of EPCs and restore their angiogenic activity in diabetes may prove to be particularly beneficial. The pre-sent review outlines current thinking on EPCs’ therapeutic potential in endothelial dysfunction in diabetes, as well as evidence-based perspectives regarding their use for vascular regenerative medicine.     

降钙素基因相关肽对糖尿病性ED大鼠阴茎海绵体平滑肌细胞表型转化的影响

目的:了解降钙素基因相关肽(CGRP)对糖尿病性ED大鼠阴茎海绵体平滑肌细胞表型转化的影响。方法:利用链脲佐菌素建立糖尿病及糖尿病性ED大鼠模型。阴茎海绵体平滑肌细胞原代培养,并进行免疫细胞化学染色鉴定。实验分为2组:正常对照组和糖尿病性ED大鼠组。不同浓度(0、10,60,100 nmol/L)CGRP作用24h后,利用qRT-PCR检测各组细胞碱性调宁蛋白和骨桥蛋白mRNA的表达。结果:各组原代培养阴茎海绵体平滑肌细胞α-肌动蛋白阳性细胞率为(95.94±0.03)%。与正常对照组比较,糖尿病组ED大鼠阴茎海绵体平滑肌细胞碱性调宁蛋白mRNA表达显著减少(4.41±0.29 vs 10.35±0.62,P<0.01),而骨桥蛋白mRNA表达水平显著上调(5.28±0.32 vs 1.32±0.24,P<0.01)。当CGRP作用的终浓度为100 nmol/L时,糖尿病组大鼠阴茎海绵体平滑肌细胞经CGRP作用后,与未经其作用相比,碱性调宁蛋白mRNA表达显著上调(6.90±0.22 vs 4.41±0.29,P<0.01),而骨桥蛋白mRNA表达水平显著减少(3.26±0.31 vs 5.28±0.32,P<0.01)。结论:CGRP可使糖尿病性ED大鼠阴茎海绵体平滑肌细胞表型从合成型向收缩型转化。     

滋阴壮阳胶囊对糖尿病性勃起功能障碍大鼠血清NO、ET-1的影响*

目的通过研究滋阴壮阳胶囊对糖尿病性勃起功能障碍(DED)大鼠血清中NO和ET-1的影响,探讨该药治疗DED的作用机制.方法雄性SD大鼠70只,60只以STZ诱导建立糖尿病(DM)模型后,通过阿朴吗啡(APO)进行阴茎勃起实验筛选DED模型,余10只为空白对照组.造模后的DED大鼠随机分成滋阴壮阳胶囊治疗组、六味地黄软胶囊对照组和模型组,在灌胃2周后,腹主动脉取血检测各组大鼠NO和ET-1.结果各组间ET-1和NO差异均有统计学意义(P<0.01);与空白对照组比较,模型组ET-1水平显著升高、NO显著下降(P<0.01);与模型组比较,治疗组和对照组均可降低ET-1水平,升高NO水平(P<0.01、P<0.05),且在降低ET-1方面治疗组优于对照组(P<0.05).结论滋阴壮阳胶囊可通过升高NO的浓度,降低ET-1的水平,重新调整ET-1与NO之间的平衡,这可能是该药治DED的机理之一.     

Platelet Indices as a marker for early prediction of erectile dysfunction in diabetic patients

Erectile dysfunction is one of the major concerns in diabetic patients. Platelet Indices including mean platelet volume, platelet count and platelet distribution width are important biomarkers for platelet activation and pathophysiology of atherothrombosis. Measurement of Platelet Indices may early predict erectile dysfunction in diabetic men. This study aimed to measure Platelet Indices in diabetic patients with erectile dysfunction and to correlate between them and erectile dysfunction especially of vasculogenic type. The study included 30 diabetic patients with diagnosed erectile dysfunction and 20 normal males as a control. Each patient was evaluated by history, International Index of Erectile Function‐5, general and local examination, HbA1c, pharmaco‐penile duplex ultrasonography and blood sample to measure Platelet Indices. Platelet distribution width and mean platelet volume were significantly higher in patients than controls (p < 0.001). Their levels were significantly higher in vasculogenic erectile dysfunction than other types (p < 0.001). No statistically significant association regards the platelet count (p > 0.05). We concluded that Platelet Indices are high in diabetic patients with erectile dysfunction especially those with vasculogenic aetiology. They can predict erectile dysfunction in diabetic men early, and so they may be considered as cheap, available and useful biomarker for early diagnosis of vasculogenic erectile dysfunction in diabetic patients.     

保护阴茎血管内皮功能:勃起功能障碍治疗新途径

阴茎勃起是典型的神经血管过程。越来越多证据表明,阴茎血管内皮功能异常是勃起功能障碍发生的重要机制。保护阴茎血管内皮功能可以改善勃起功能,血管内皮保护剂通过减轻氧化应激损伤、保护勃起递质的功能活性,改善阴茎海绵体血管内皮功能,从而治疗勃起功能障碍。保护阴茎血管内皮功能,将成为勃起功能障碍治疗的新途径。     

Melatonin prevents deterioration of erectile function in streptozotocin-induced diabetic rats via sirtuin-1 expression

A review of the literature indicated that sirtuin-1 expression, a regulator of nitric oxide bioavailability in erectile dysfunction (ED) after melatonin therapy, has not yet been investigated. The objective of this study was to evaluate the protective effects of melatonin for erectile function with sirtuin-1 protein expression in type 1 diabetic rat models. Fifty male Sprague Dawley rats were placed into five groups. Except for those in the control group (C), each animal received a single dose (60 mg/kg) of streptozotocin to induce diabetes. The animals were placed into the diabetes (D) group, insulin (I) group (6 U/kg/day), melatonin (Mel) group (10 mg kg⁻¹ day⁻¹) and combined treatment (I + Mel) group. Ten weeks later, the serum testosterone levels, intracavernosal pressure (ICP), mean arterial pressure (MAP), malondialdehyde (MDA), cyclic guanosine monophosphate (c-GMP), 8-hydroxydeoxyguanosine (8-OHdG), nitric oxide synthase (NOS), caspase-3 activity, sirtuin-1 and endothelial nitric oxide synthase (eNOS) protein expression and histological findings were assessed. The mean ICP/MAP ratio for the D group was lower than the mean ratios for the other groups. The treatment groups, particularly the I + Mel group, exhibited lower 8-OHdG and MDA levels and caspase-3 activity than the D group. The sirtuin-1 and eNOS expression and cavernosal tissue (CT) histology seemed to have been preserved by the melatonin and/or insulin therapy. These results were indicative of a profound protective effect of melatonin by the activation of sirtuin-1 protein expression against hyperglycemia-induced oxidative CT injury.     

糖尿病性阴茎勃起功能障碍动物模型血清雄激素测定

ＳＤ大鼠注射链脲佐菌素制造溏尿病（ＤＭ）动物模型后,注射阿朴吗啡观察不同时期大鼠阴茎勃起情况,筛选ＤＭ性阴茎勃起功能障碍（ＥＤ）大鼠模型,测定其血清ＬＨ、ＦＳＨ及睾酮的浓度,并观察睾丸组织的显微结构,研究ＤＭ性ＥＤ的发病机理。结果ＤＭ性ＥＤ大鼠血清睾酮浓度显著降低,睾丸组织显微结构发生明显病理性改变,且上述变化与ＤＭ病程密切相关;ＬＨ在ＤＭ早期无改变、晚期明显降低;ＦＳＨ无明显改变。提示ＤＭ严重影阴茎勃起功能及雄激素的合成分泌,雄激素降低可能是其主要发病机理之一。     

负压吸引对糖尿病性ED大鼠阴茎海绵体组织一氧化氮合酶表达的影响

目的研究负压吸引对糖尿病性勃起功能障碍（ED）大鼠阴茎组织一氧化氮合酶（NOS）表达水平的影响。方法25只实验鼠中随机选取5只为正常对照组（A组）,其余火鼠用链脲左菌素和阿朴吗啡诱导建立Ⅰ型糖尿病性ED大鼠模型。之后把造模成功的糖尿病性ED大鼠随机分成糖尿病ED吸引组（B组）和糖尿病ED非吸引组（C组）。在B组大鼠负压吸引治疗结束后将A、B、C3组大鼠处死并取阴茎组织进行石蜡包埋。采用免疫组织化学方法检测各组大鼠阴茎组织中三种一氧化氮合酶亚型（nNOS、eNOS、iNOS）的表达情况。结果A组大鼠阴茎组织中nNOS蛋白表达水平高于B组和C组（均P〈0.001）;A组和B组大鼠阴茎组织中eNOS蛋白表达水平高于C组（均P〈0.01）;A组iNOS蛋白表达水平低于B组和C组（P〈0.01,P〈0.001）,同时B组iNOS蛋白表达水平低于C组（P〈0.01）;剩余其他各组间的比较差异无统计学意义（P〉0.05）。结论负压吸引可以通过升高阴茎组织中的eNOS和降低iNOS的表达来改善勃起功能。     

Stem cells: novel players in the treatment of erectile dysfunction

Stem cells are defined by their capacity for both self-renewal and directed differentiation; thus, they represent great promise for regenerative medicine. Historically, stem cells have been categorized as either embryonic stem cells (ESCs) or adult stem cells (ASCs). It was previously believed that only ESCs hold the ability to differentiate into any cell type, whereas ASCs have the capacity to give rise only to cells of a given germ layer. More recently, however, numerous studies demonstrated the ability of ASCs to differentiate into cell types beyond their tissue origin. The aim of this review was to summarize contemporary evidence regarding stem cell availability, differentiation, and more specifically, the potential of these cells in the diagnosis and treatment of erectile dysfunction (ED) in both animal models and human research. We performed a search on PubMed for articles related to definition, localisation and circulation of stem cells as well as the application of stem cells in both diagnosis and treatment of ED. Strong evidence supports the concept that stem cell therapy is potentially the next therapeutic approach for ED. To date, a large spectrum of stem cells, including bone marrow mesenchymal stem cells, adipose tissue-derived stem cells and muscle-derived stem cells, have been investigated for neural, vascular, endothelial or smooth muscle regeneration in animal models for ED. In addition, several subtypes of ASCs are localized in the penis, and circulating endogenous stem cells can be employed to predict the outcome of ED and ED-related cardiovascular diseases.     

The administration of folic acid improves erectile function and reduces intracavernosal oxidative stress in the diabetic rabbit

OBJECTIVE

To test the possibility that folic acid (FA) may be a means of treating erectile dysfunction (ED) in diabetes mellitus (DM), by studying the effect of FA administration to DM rabbits on cavernosal function and intrapenile oxidative stress.

MATERIALS AND METHODS

To investigate the effect of administering FA to DM rabbits on erectile function and oxidative stress the formation of superoxide (O₂^‐), 8‐isoprostane F_2α (8‐IPF_2α) and prostacyclin (as 6‐keto‐PGF_1α) were assessed, as well as carbachol‐ and electrical field stimulated (EFS) relaxation and p47^phox content (active component of NADPH oxidase complex). Non‐ketotic DM was induced in New Zealand rabbits with alloxan and FA administered orally daily for 1 month. Rabbits were killed, penises excised and segments prepared. These were mounted in an organ bath and relaxation elicited with carbachol or EFS. O₂^‐ release was measured spectrophotometrically, p47^phox expression by Western blotting and 8‐IPF_2α and 6‐keto‐PGF_1α formation by enzyme‐linked immunosorbant assay. Blood was collected for measurement of homocysteine, red blood cell (RBC) folate and glucose.

RESULTS

In cavernosal tissue from DM rabbits, carbachol‐and EFS‐induced relaxation was significantly impaired compared with the untreated controls. O₂^‐ release, p47^phox expression and 8‐IPF_2α formation were all enhanced and 6‐keto‐PGF_1α formation reduced compared with the controls. All these effects were reversed by FA. Plasma total homocysteine was reduced and RBC folate elevated.

CONCLUSIONS

The administration of FA may constitute a strategy for reducing ED in patients with DM.     

Probucol improves erectile function by regulating endoplasmic reticulum stress in rats with streptozotocin-induced diabetes

This study was to explore the effect and mechanism of Probucol on STZ-induced erectile dysfunction in diabetic rats. Thirty SD male rats aged 12 weeks were given intraperitoneal injection of STZ after fasting for 12 hr. Diabetic rats were haphazardly partitioned under two assemblies and administered 0 or 500 mg/kg probucol by oral gavage to 12 weeks. Control group was intraperitoneally injected with physiological saline, and saline was administered by oral gavage daily. Intracorporeal pressure was used to evaluate erectile function. Levels of proteins were detected using immunohistochemistry and Western blotting. α-SMA and vWF were detected using immunofluorescence staining. After treatment, erectile function in probucol group was significantly improved. Endoplasmic reticulum stress-related proteins were expressed higher in DM group than in sham group, while expression of these proteins decreased significantly in probucol group. However, α-SMA and vWF were expressed at lower levels in DM group than in sham group, and probucol treatment reversed this phenomenon. Finally, Bax and Caspase3 were expressed at higher levels and Bcl-2 was expressed at lower levels in DM group, while the opposite result was obtained in probucol group. In conclusions, probucol improves erectile function by reducing endothelial dysfunction and inhibiting PERK/ATF4/CHOP pathway in STZ-induced diabetic rats.