糖尿病大鼠阴茎海绵体组织中一氧化氮合酶亚型表达的研究

目的:通过观察糖尿病性雄性大鼠阴茎海绵体组织中一氧化氮合酶亚型(nNOS、iNOS、eNOS)表达和勃起功能的变化,以及应用胰岛素、α-硫辛酸(LA)干预对其的影响,进一步探讨糖尿病性ED发病机制,并为临床治疗提供新的思路。方法:将50只成年雄性SD大鼠分为4组:A组为正常对照组(10只),B组为糖尿病无干预组(13只),C组为糖尿病胰岛素干预组(12只),D组为糖尿病胰岛素+LA干预组(15只),采用腹腔注射链脲佐菌素法制作糖尿病模型。8周后各组大鼠通过注射阿朴吗啡后评价勃起功能并取阴茎海绵体组织用免疫组化EnV i-sion法观察海绵体组织中nNOS、iNOS、eNOS表达的变化。结果:A组大鼠勃起功能正常,勃起率100%;与A组相比,B组、C组、D组勃起功能水平显著降低(P<0.05),勃起率:B组28.6%,C组62.5%,D组80.9%,其海绵体组织中nNOS、eNOS表达显著降低,A组大鼠海绵体组织每视野nNOS、eNOS阳性神经纤维数为86.7、9.6,B组为36.5、3.3,C组为52.7、5.7,D组为71.4、7.4,而iNOS表达显著增加(P<0.05),A组为6.9,B组为43.6,C组为36.2,D组为19.3;与B、C组相比,D组勃起功能显著上升,海绵体组织中nNOS、eNOS表达均显著上升,iNOS显著下降(P<0.05)。结论:糖尿病严重影响阴茎勃起功能和nNOS、iNOS、eNOS的表达,高血糖是其发病基础之一,而LA对其有显著疗效,推测可能与其抗氧化作用机制有关。     

骨髓间充质干细胞即刻与延时治疗修复阴茎海绵体神经损伤大鼠勃起功能的研究

目的:拟观察在双侧阴茎海绵体神经(CN)损伤的大鼠神经性勃起功能障碍(NED)模型中即刻和延时向阴茎海绵体注射骨髓间充质干细胞(BM-MSCs)对大鼠阴茎勃起功能的修复作用。方法:选取28只8周龄、体重200~250 g雄性SD大鼠随机分为4组:假手术组找到双侧海绵体神经后不做处理直接关腹并缝合皮肤;对照组、即刻治疗组和延时治疗组均通过钳夹的方式损伤双侧阴茎海绵体神经建立NED模型随后关腹缝合。假手术组和对照组向阴茎海绵体内注射对照剂,即刻治疗组注射BM-MSCs,延时治疗组术后两周注射BM-MSCs。术后12周采用电刺激CN记录阴茎海绵体内压(ICP),颈动脉穿刺测定平均动脉压(MAP),ICP/MAP作为勃起功能的评价指标来评估大鼠的勃起功能。在勃起功能检测后处死大鼠,取阴茎海绵体中段组织检测平滑肌、胶原和神经纤维。结果:在手术后12周,即刻治疗组和延时治疗组ICP和ICP/MAP均较对照组升高(P0.05)。即刻治疗组和延时治疗能提高大鼠海绵体组织内平滑肌与胶原的比例(P0.05),同时两组阴茎海绵体内平滑肌含量高于对照组(P0.05),阴茎海绵体背神经内神经微丝(NF)蛋白阳性神经纤维数目和nNOS的表达高于对照组(P0.05)。结论:阴茎海绵体内注射BM-MSCs能对双侧CN损伤大鼠的勃起功能恢复有促进作用。BM-MSCs治疗可以提高海绵体组织内平滑肌与胶原的比例,改善纤维化,并能提高海绵体组织中平滑肌含量、阴茎背神经的神经丝含量和nNOS的表达水平,术后延时治疗同样能取得一定的治疗效果。     

FK506对大鼠阴茎海绵体神经再生影响的研究

目的:探讨FK506对大鼠阴茎海绵体神经损伤后再生的影响,并讨论其作用的可能机制。　方法:54只 SD雄性大鼠随机分成3组,即假手术对照组(简称对照组,n=24)、单侧阴茎海绵体神经切断组(简称单切组,n= 24)、单侧阴茎海绵体神经切断+FK506组(简称FK506组,n=6)。术后1、3个月电刺激阴茎海绵体神经并连续监 测阴茎海绵体内压变化及阴茎勃起情况,同时取阴茎海绵体组织采用NADPH d法观察一氧化氮合酶(nNOS)阳性 神经纤维的再生情况。　结果:术后1个月单切组nNOS阳性神经纤维数量明显减少,与对照组相比差异有极显 著性(P<0.01),术后3个月在电刺激未切断侧阴茎海绵体神经时,FK506组比单切组产生更大的最大海绵体内压 (P<0.01),且单切组阴茎海绵体组织中nNOS阳性神经纤维比术后1个月无明显增加(P>0.05),而FK506组 nNOS阳性神经纤维显著增加(P<0.01)。　结论:FK506皮下注射能促进大鼠损伤的阴茎海绵体神经再生,促进 勃起功能恢复。     

糖尿病鼠周围神经和阴茎nNOS的表达及其与阴茎勃起功能的关系

目的研究糖尿病(Diabetes mullitus,DM)对大鼠坐骨神经、阴部神经及阴茎海绵体中神经型一氧化氮合酶(nNOS)变化及其与勃起功能障碍的相关性。方法16只雄性大鼠随机分为2组：12周组和16周组各8只,腹腔注射链脲佐菌素制备糖尿病模型：另取8只注射枸檬酸缓冲液作为空白对照,分别在注射12周和16周后,观察大鼠阴茎勃起功能,采用免疫组织化学法检测DM大鼠坐骨神经、阴部神经和阴茎海绵体nNOS阳性神经纤维的表达。结果两组大鼠的阴茎勃起次数明显低于对照组大鼠,(P＜0．01)；16W组大鼠阴茎勃起次数也明显低于12周组大鼠(P＜0．05)。两组DM大鼠nNOS坐骨神经、阴部神经和阴茎海绵体中nNOS的表达明显低于对照组(P＜0．01)；16W糖尿病大鼠nNOS阳性纤维的表达也明显低于12周组。两组大鼠对照组间无显著差异。结论糖尿病性阴茎勃起功能障碍与nNOS阳性神经纤维数量的减少相关,可能为糖尿病性勃起功能障碍的发病机理之一。     

自体盆神经节海绵体内移植对大鼠阴茎nNOS的影响

双侧海绵体神经离断后几乎无一例外发生勃起功能障碍 (ED) ,原因主要是阴茎海绵体内含神经性一氧化氮合酶(nNOS)神经纤维明显减少[1] 。我们通过动物实验研究一侧盆神经节的海绵体内移植对阴茎去神经支配后海绵体内nNOS的变化 ,探讨神经元移植治疗神经性ED的可能性。材料与方法　SD雄性大鼠 36只 ,3～ 6月龄 ,体重 30 0～ 4 0 0g。随机分为盆神经节移植实验组 :切断双侧海绵体神经并将左盆神经节移植入左侧阴茎脚并标记 ;双侧海绵体神经离断组以及正常对照组。 6周及 12周末脱颈椎法处死大鼠 ,迅速取各组阴茎中段海绵体组织以及实验组…     

糖尿病大鼠阴茎海绵体组织nNOS神经变化的实验研究

目的 :研究糖尿病对大鼠阴茎海绵体组织nNOS神经纤维的影响。　方法 :34只SD雄性大鼠分为 6周组(17只 )和 8周组 (17只 ) ,其中每组各 11只腹腔注射链脲佐菌素制备糖尿病模型 ,其余各 6只注射柠檬酸缓冲液作为空白对照 ,分别在注射 6周和 8周后 ,观察大鼠阴茎勃起功能 ,并采用免疫组化SP法检测糖尿病大鼠阴茎组织nNOS神经纤维的数量。　结果 :2组糖尿病大鼠的阴茎勃起率分别为 37.5 %和 14 .3% ,差异有显著性 (P <0 .0 5 ) ,均明显低于对照组 (P <0 .0 1)。 2组糖尿病大鼠nNOS神经纤维的表达明显低于对照组 (P <0 .0 1)。 8周组中糖尿病大鼠阴茎的勃起功能和nNOS神经纤维的数量明显低于 6周组 ,分别为 (37.6 0± 6 .76 )条和 (2 8.0 0±5 .2 9)条 ,即随着病程的延长 ,勃起功能和nNOS神经纤维的表达下降 (P <0 .0 5 ) ,而对照组大鼠nNOS神经纤维的数量差异无显著性 [(83.0 0± 3.2 2 )vs(81.0 0± 3.6 1) ]。　结论 :糖尿病严重影响勃起功能和nNOS神经纤维的表达。糖尿病大鼠阴茎海绵体组织中nNOS神经纤维的数量明显减少 ,且与病程正相关 ,这可能是糖尿病性勃起功能障碍的发病机理之一。     

生长激素补充对老龄大鼠勃起功能及阴茎海绵体nNOS表达的影响

目的探讨生长激素(GH)补充对老龄大鼠勃起功能及阴茎海绵体神经型一氧化氮合酶(nNOS)表达的影响。方法20只18月龄SD大鼠随机均分成A、B两组,10只2月龄SD大鼠为C组。A组给予GH1U/(kg·d),B、C组给予相同剂量的生理盐水,均皮下注射8周。于8周末观察阿朴吗啡(APO)皮下注射与大鼠海绵体内注射罂粟碱诱导的阴茎勃起情况,并用免疫组化SP法检测阴茎海绵体组织中nNOS神经纤维的数目。结果8周末时,A、C组大鼠APO诱导的勃起次数、海绵体内注射罂粟碱诱导的最大海绵体内压以及阴茎海绵体组织中nNOS神经纤维数目均显著高于B组(P<0.05或P<0.01)。结论老龄大鼠勃起功能及阴茎海绵体nNOS表达较成年大鼠明显下降,GH补充可以部分改善老龄大鼠的勃起功能,其机制之一可能与GH补充增加了老龄大鼠阴茎海绵体组织中nNOS神经纤维数目有关。     

伊木萨克片对糖尿病性ED大鼠阴茎组织中eNoS和nNoS的影响

目的 研究维药伊木萨克片对DM性ED大鼠阴茎海绵体组织中eNOS和nNOS蛋白表达水平的影响.方法 取雄性SD大鼠70只,从中随机取10只为正常对照组,余60只以链脲佐菌素诱导建立DM模型后,行阿朴吗啡阴茎勃起实验筛选DM性ED模型,发生ED者随机分为DM性ED组、伊木萨克片组、胰岛素组、伊木萨克片 胰岛素(联用)组,未成DM者为STZ组.各组给药6周后,采用免疫组化SP法检测各组大鼠阴茎组织中eNOS、nNOS含量.结果 DM性ED组大鼠阴茎组织中eNOS、nNOS蛋白表达水平显著低于正常对照组(P＜0.01);伊木萨克片组、胰岛素组及联用组大鼠阴茎组织中eNOS、nNOS蛋白表达水平均显著高于DM性ED组(P＜0.01),但伊木萨克片组与胰岛素组显著低于联用组(P＜0.01, P＜0.01;P＜0.05,P＜0.01);STZ组与正常对照组之间的差异则无统计学意义(P＞0.05).结论 维药伊木萨克片可以显著提高DM性ED大鼠阴茎组织中eNOS、nNOS蛋白表达水平,并提示在胰岛素控制血糖的基础上效果可能更佳.     

生殖股神经移植重建大鼠勃起神经通道

目的　探讨利用生殖股神经移植加神经生长强化介质修复损伤的阴茎海绵体神经,重建勃起神经通道的可行性。　方法　3月龄SD雄性大鼠54只,随机平均分成假手术对照组、双侧阴茎海绵体神经损伤组及神经移植加胰岛素样神经生长因子Ⅰ(IGF Ⅰ)组。术后1、3、6个月用阿朴吗啡试验评估各组动物勃起功能,并取阴茎干组织,采用NADPH d组化法了解nNOS阳性神经纤维的再生情况。　结果　术后1、3、6个月,假手术对照组均有正常阴茎勃起(勃起率100% ),神经切断组完全丧失勃起功能(勃起率0% );术后1个月神经移植组也丧失勃起功能(勃起率0% ),术后3、6个月勃起功能渐恢复(勃起率分别为50%和66. 7% ),两两比较差异有统计学意义(P<0. 05)。术后3、6个月,神经移植组nNOS 阳性神经纤维数显著增多,神经部分切断组的nNOS阳性神经纤维数和术后1个月相比无增多,两两比较差异有统计学意义(P<0. 002)。　结论　双侧阴茎海绵体神经损伤后,利用生殖股神经移植加IGF促进神经再生,是重建勃起神经通路,恢复大鼠勃起功能的一种有效方法。     

神经套管术重建勃起功能的动物实验研究

目的　探讨利用神经套管术加神经生长强化介质修复阴茎海绵体神经损伤 ,重建勃起功能的可行性。　方法　 5 4只SD雄性大鼠随机分成假手术对照组、双侧阴茎海绵体神经损伤组及神经套管加胰岛素生长因子 (IGF)组 ,术后 1、3、6个月用阿朴吗啡试验评估所建动物模型的勃起功能 ,随后取阴茎干、脚组织 ,利用NADPH d染色法证实nNOS阳性神经纤维的再生情况。　结果　术后 1个月 ,阿朴吗啡诱导阴茎勃起试验中 ,神经部分切断组和神经套管IGF组间勃起率没有显著差异 ;术后 3、6个月 ,神经套管组勃起率分别为 4 2 %和 5 0 % ,神经部分切断组勃起率均值为 0 % (P <0 .0 5 )。术后 3、6个月 ,神经套管组nNOS阳性神经纤维数显著增多 ,神经部分切断组的nNOS阳性神经纤维数同术后 1个月相比无增多 (P <0 .0 0 2 ) ,两两比较差异有显著性意义。　结论　利用神经套管加IGF促进神经再生 ,是双侧阴茎海绵体神经损伤后 ,重建勃起功能的一种有效方法。     

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。     

Differential expression of neurotrophins in penises of streptozotocin-induced diabetic rats

To explore the mechanism of diabetic erectile dysfunction, we studied the distribution of neurotrophins in the penises of diabetic rats, including nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Male Sprague-Dawley rats were injected with 65 mg/kg streptozotocin to induce diabetes mellitus (DM). The control rats were raised as age-matched control. Eight weeks later, the intercavernous pressure (ICP) of the rats was measured after electrostimulation and before sacrifice. Each peeled penis was divided into 2 parts, one for immunohistochemistry and the other for Western blot analysis. The ICP of the DM group rats was significantly decreased as compared to the vehicle control rats. There were significantly more NGF-positive neurons in the penises of the diabetic rats than in those of the control rats, while the opposite results were observed for BDNF-positive neurons. In the Western blot analysis, the proteins of NGF, NT-3, and NT-4 were all increased, while that of BDNF was decreased in diabetic rats. This is the first study revealing the expression of NT-4 protein in cavernous tissue. The abnormal level of these 4 neurotrophins in cavernous tissue may be one of the factors of the pathogenesis of diabetic ED. The increase of neurotrophins may reflect the degree of cavernous tissue denervation and may represent a compensatory mechanism. The lesion of the retrograde axonal transport of the nerves caused by hyperglycemia may be related to this phenomenon.     

Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model.

Erectile dysfunction occurs frequently in humans with diabetes mellitus; the molecular basis of this phenomenon is not known. We investigated the effects of diabetes on penile erection, nitric oxide synthase and growth factors expression in an animal model. Forty male rats were divided into two groups: the experimental group (n = 30) received intraperitoneal injection of Streptozotocin (STZ) dissolved in citrate buffer to induce diabetes; ten age-matched control rats received injection of citrate buffer vehicle only. Before euthanization at eight weeks, erectile function was assessed by electrostimulation of the cavernous nerves. NADPH diaphorase staining was used to identify NOS and immunostaining technique was used to identify nNOS in the penile nerve fibers. RT-PCR was used to identify mRNA expression of nNOS, eNOS, iNOS, ER-beta, ER-alpha, NGF, IGF-I, TGF-beta 1, and AR. Western blot was used to identify nNOS, IGF-I, NGF, and TFG-beta protein expressions. In the diabetic group, there was: (1) a significant decrease in NOS containing nerve fibers in the dorsal and intracavernosal nerves; (2) a significant lower maximal intracavernosal pressure. RT-PCR showed down-regulation of nNOS (large form), iNOS and ER-beta mRNA expression, Immunoblot showed down-regulation of nNOS protein expression and nNOS immunostaining showed less positive staining in the dorsal and intracavernous nerves in the diabetic group. These molecular changes may provide the basis for further studies to explore the association between diabetes and impotence.     

Neurotrophic effect of bone marrow mesenchymal stem cells for erectile dysfunction in diabetic rats

It has been demonstrated that intracavernous injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) had beneficial effects on improving erectile function in type-1 diabetic rats. This study was designed to investigate the neurotrophic effect of BM-MSCs for type-1 diabetic rats. Streptozocin-induced type-1 diabetic rats were randomly divided into three groups: diabetic group, BM-MSCs-treated group and BM-MSCs-conditioned medium-treated group. At the 3d, 1 and 2w time points after BM-MSCs injection, three randomly selected rats in MSCs group were sacrificed and penile samples were harvested to detect BM-MSCs in penile tissue. Four weeks after intracavernous injection of BM-MSCs or BM-MSCs-conditioned medium, intracavernous pressure (ICP) was assessed to evaluate the erectile function. Immunohistochemistry was used to track labelled BM-MSCs in penile tissue and to detect neuronal nitric oxide synthase (nNOS) and neurofilament (NF) positive fibres in penile dorsal nerve. Enzyme lined immunosorbent assay (ELISA) was used to measure the concentrations of vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in BM-MSCs-conditioned medium. BM- MSCs secreted detectable levels of VEGF, BDNF and NGF. Intracavernous injection of BM-MSCs improved erectile function in diabetic rats. The functional improvement was accompanied by promoted nNOS and NF positive nerve fibres within penile dorsal nerve in type-1 diabetic rats. Histological data revealed a time-dependent decrease in the number of BM-MSCs in the corpus cavernosum following injection. Furthermore, the beneficial effect of BM-MSCs was partially repeated by BM-MSCs-conditioned medium. Intracavernous injection of BM-MSCs is effective in improving nerve regeneration in diabetic rats. Paracrine effects of BM-MSCs are probably involved in the improvement.     

Expression of oxytocin receptor in diabetic rat penis

Oxytocin receptor (OTR) expressed in the rat penis and mediated the contractility of the corpus cavernosum smooth muscle both in vitro and in vivo, and OTR could maintain penile detumescence; however, the expression of OTR in diabetic rat penis remains unknown. In the present study, we investigated the expression of OTR in diabetic rat penis. The experimental rats were randomly divided into control group and STZ-diabetic rats group. The expressions of mRNA and protein were examined by real-time quantitative PCR, Western blotting and immunohistochemistry respectively. Erectile function was evaluated by measuring intracavernous pressure following electrostimulation of the cavernous nerves. mRNA and protein expression of OTR significantly increased in diabetic rats group compared with the control group. Erectile function of diabetic rats group significantly decreased compared with the control group. Our data showed that the expression of OTR significantly increased in diabetic rats group and OTR may involve in the development of diabetic erectile dysfunction.     

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.     

Effect of diabetes and insulin treatment on nitric oxide synthase content in rat corpus cavernosum

AIM: To study the effect of diabetes mellitus and insulin treatment on rat penile nitric oxide synthase content. METHODS: Male Wistar rats were divided at random into two groups: the Control (n = 8) and the Diabetic (n = 17). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The diabetic animals were then randomly divided into two subgroups: diabetic rats without insulin treatment (n = 7) and diabetic rats with insulin treatment (n = 10). The neuronal nitric oxide synthase (nNOS) in the penile corpus cavernosum were assayed by immumohistochemical staining with specific antibody to nNOS and the nNOS-positive nerve fibers were counted semiquantitatively under a high power microscope. RESULTS: The nNOS- positive nerve fibres in diabetic rats with treatment was higher than that in diabetic rats without treatment (P < 0.05) and lower than that in the controls (P < 0. 01). The nNOS-positive nerve fibres in diabetic rat without treatment were also lower than that in the controls (P < 0. 01). CONCLUSION: In streptozotocin-induced diabetic rats, the nNOS content in the penile corpus cavernosum was significantly decreased. Insulin treatment at the dose level employed partially restores the penile nNOS content in these rats.     

Gene transfer of endothelial nitric oxide synthase partially restores nitric oxide synthesis and erectile function in streptozotocin diabetic rats

PURPOSE: We determined whether adenoviral gene transfer of endothelial nitric oxide synthase (eNOS) to the penis of streptozotocin induced diabetic rats could improve the impaired erectile response. MATERIALS AND METHODS: Two experimental groups of animals were transfected with adenoviruses, including streptozotocin (Sigma Chemical Company, St. Louis, Missouri) diabetic rats with AdCMVbetagal and streptozotocin diabetic rats with AdCMVeNOS. At 1 to 2 days after transfection these study animals underwent cavernous nerve stimulation to assess erectile function and their responses were compared with those of age matched control rats. In control and transfected streptozotocin diabetic rats eNOS and neuronal NOS (nNOS) were examined by Western blot analysis. Constitutive and inducible NOS activities were evaluated in the presence and absence of calcium by L-arginine to L-citrulline conversion and nitrate plus nitrite levels were measured. In control and streptozotocin diabetic penes beta-galactosidase activity and localization were determined. RESULTS: After transfection with AdCMVbetagal beta-galactosidase was localized to the endothelium and smooth muscle cells of the streptozotocin diabetic rat penis. Streptozotocin diabetic rats had a significant decrease in erectile function, as determined by peak and total intracavernous pressure (area under the curve) after cavernous nerve stimulation compared with control rats. Streptozotocin diabetic rats transfected with AdCMVeNOS had peak intracavernous pressure and area under the curve similar to those in control animals. This change in erectile function was a result of eNOS over expression with an increase in eNOS protein expression and constitutive NOS activity as well as an increase in nitric oxide biosynthesis, as reflected by an increase in cavernous nitrate plus nitrite formation. There was no change in nNOS protein expression or calcium independent conversion of NOS (inducible NOS activity). CONCLUSIONS: Adenoviral gene transfer of eNOS significantly increased peak and total intracavernous pressure to cavernous nerve stimulation in streptozotocin diabetic rats to a value similar to the response observed in control rats. Our results suggest that eNOS contributes significantly to the physiology of penile erection. These data demonstrate that in vivo adenoviral gene transfer of eNOS can physiologically improve erectile function in the streptozotocin diabetic rat.     

Effect of diabetes and insulin treatment on nitric oxide synthase content in rat corpus cavemosum

Aim: To study the effect of diabetes mellitus and insulin treatment on rat penile nitric oxide synthase content.Methods: Male Wistar rats were divided at random into two groups: the Control (n = 8) and the Diabetic (n =17). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The diabetic animals were then ran-domly divided into two subgroups; diabetic rats without insulin treatment (n = 7) and diabetic rats with insulin treat-ment (n = 10). The neuronal nitric oxide synthase (nNOS) in the penile corpus cavernosum were assayed by immumo-histochemical staining with specific antibody to nNOS and the nNOS-positive nerve fibers were counted semiquantita-tively under a high power microscope. Results: The nNOS- positive nerve fibres in diabetic rats with treatment washigher than that in diabetic rats without treatment ( P < 0.05) and lower than that in the controls ( P < 0.01). ThenNOS-positive nerve fibres in diabetic rat without treatment were also lower than that in the controls (