腺病毒介导PDE5A1反义核酸改善糖尿病兔阴茎勃起功能的实验研究

目的探讨腺病毒介导PDE5A1反义核酸对海绵体平滑肌PDE5基因表达的抑制作用及对兔阴茎勃起功能的影响.方法25只成年雄性新西兰兔随机分为5组1组为正常对照组,4组静脉注射四氧嘧啶建立糖尿病性勃起功能障碍(ED)动物模型,分别将携带反义基因腺病毒载体、携带β-半乳糖苷酶基因腺病毒载体(β-gal组)、空载体及0.9%NaCl转染模型组阴茎海绵体.转染后第7天,电刺激盆神经测定各组阴茎海绵体内压(NSICP),评价阴茎勃起功能,ELISA法测定海绵体组织cGMP浓度,Western blot法分析海绵体组织中β-gal表达水平.结果反义核酸组海绵体组织cGMP浓度(25.6±2.5)fmol/mg蛋白,明显高于β-gal组(8.8±0.9)fmol/mg蛋白、空载体组(8.3±1.1)fmol/mg蛋白和糖尿病对照组(7.4±0.8)fmol/mg蛋白,差异有统计学意义(P＜0.05);反义核酸组NSICP增加幅度(66.2±3.6)mmHg,明显高于β-gal组(38.2±2.5)mmHg、空载体组(35.2±2.2)mmHg及糖尿病对照组(36.6±2.7)mmHg,差异有统计学意义(P＜0.05);与正常对照组(65.2±3.2)mmHg比较差异无统计学意义(P＞0.05);β-gal组海绵体组织β-gal表达水平明显高于其他组.结论腺病毒介导PDE5A1反义基因能改善糖尿病兔阴茎勃起功能,PDE5A1可作为ED基因治疗的重要靶基因.     

静脉炎动物模型的建立及TNF-α、ICAM-1的表达

目的建立静脉炎动物模型,探讨静脉炎形成机制,为其防治方法提供依据。方法将10只新西兰大耳兔随机分为正常对照组和模型组各5只。模型组选用美国BD公司生产的静脉留置针在兔双耳缘静脉行留置针静脉穿刺置管,连续5d静脉注射甘露醇10mL并在15min内完成,以形成条索状静脉(Ⅲ级静脉炎)为观察指标,拔除留置针,腹腔麻醉下活体留取标本。正常对照组不进行静脉留置,但同样进行双耳包扎,共5d,腹腔麻醉下活体留取标本。结果模型组与正常对照组相比,肿瘤坏死因子α(TNF-α)蛋白及细胞间黏附分子1(ICAM-1)蛋白表达显著增加(均P0.01)。结论连续注射甘露醇能形成兔耳缘静脉静脉炎,其形成机制与TNF-α、ICAM-1表达上调有关。     

不同部位静脉注射阿霉素对兔心功能的影响

目的 探讨不同部位静脉注射阿霉素对处于亚临床阶段心功能的影响.方法 将18只家兔随机分为实验组(12只)和对照组(6只),实验组从耳缘静脉推注阿霉素2 mg/kg,1次/周,连续4周制成动物模型;对照组按同样方法推注等量生理盐水.于末次给药后4周,再将实验组分为实验1组和2组各6只,分别从耳缘静脉和中心静脉注射阿霉素2 mg/kg;对照组从耳缘静脉推注等量生理盐水.结果 实验组表现为阿霉素心肌毒性的特征,对照组正常;实验2组心功能指标较实验1组和对照组改变显著.结论 从回心路径短的部位给予阿霉素可导致心脏毒性,使处于亚临床阶段的心脏收缩功能下降.     

不同部位静脉注射阿霉素对兔心功能的影响

目的探讨不同部位静脉注射阿霉素对处于亚临床阶段心功能的影响。方法将18只家免随机分为实验组（12只）和对照组（6只），实验组从耳缘静脉推注阿霉素2mg／kg，1次／周，连续4周制成动物模型；对照组按同样方法推注等量生理盐水。于末次给药后4周，再将实验组分为实验1组和2组各6只，分别从耳缘静脉和中心静脉注射阿霉素2mg／kg；对照组从耳缘静脉推注等量生理盐水。结果实验组表现为阿霉素心肌毒性的特征，对照组正常；实验2组心功能指标较实验1组和对照组改变显著。结论从回心路径短的部位给予阿霉素可导致心脏毒性，使处于亚临床阶段的心脏收缩功能下降。     

甲强龙联合脂多糖诱导兔股骨头坏死模型的建立

目的观察甲强龙联合脂多糖诱导兔股骨头坏死的实验效果。方法 30只健康雄性新西兰兔,随机分为实验组(20只)和对照组(10只),实验组耳缘静脉注射脂多糖(lipopolysaccharides,LPS)10μg/kg,24 h后肌注甲强龙20 mg/kg,1次/d,共3 d。对照组注射同等剂量的生理盐水。6周后观察兔股骨头X射线、磁共振及病理学等指标的改变。结果对照组X线:双侧股骨头骨皮质完整,大小及形态正常,骨密度均匀,骨小梁清晰;实验组X线:兔股骨头密度减低,骨小梁模糊不清,可见一囊状透亮区,股骨头保持完整;MRI示:股骨头见一类圆形高信号影,边界相对清晰,关节面完整;病理:骨小梁纤细,部分骨小梁断裂,髓腔内造血细胞减少,脂肪细胞体积增大,有的融合成泡状。结论甲强龙联合脂多糖能够成功安全便捷地诱导兔股骨头坏死动物模型。     

IGF-1基因治疗提高老龄大鼠阴茎海绵体平滑肌密度的研究

目的 观察阴茎海绵体内注射胰岛素样生长因子-1 (IGF-1)基因能否提高老年性大鼠阴茎勃起功能及其对阴茎海绵体平滑肌密度的影响,以探讨IGF-1基因治疗ED的机制.方法 4月龄SD雄性大鼠(青年组)10只;24月龄SD雄性大鼠(老龄组)20只,随机分为2组:PBS对照组、100 μg IGF-1质粒注射组.每组10只注射后8周行电刺激检测大鼠阴茎海绵体内压(ICP)和平均动脉压(MAP),分析比较IGF-1基因治疗的效果,Masson,s三色染色图文定量分析阴茎海绵体平滑肌在海绵体组织中含量的变化.结果 电刺激发现老龄组较青年组ICP/MAP和总ICP明显降低(P＜0.05).IGF-1基因治疗8周后,100 μg IGF-1质粒注射组较PBS对照组ICP/MAP和total ICP均明显提高(P＜0.05);阴茎海绵体平滑肌的含量在老龄组较青年组明显降低(P＜ 0.05);与PBS对照组比较,100μg IGF-1质粒注射组能够明显提高阴茎海绵体平滑肌的含量(P＜0.05).结论 I GF-1基因治疗能够改善老龄大鼠的勃起功能,其作用机制之一可能是通过提高阴茎海绵体平滑肌的含量.     

微型高频针状电极刺激辅助活体软骨重塑形的初步研究

目的初步观察微型高频针状电极刺激兔耳软骨组织后的组织形态学变化,探讨其作为耳畸形矫治方法的可行性。方法 5～6月龄雄性新西兰白兔5只,将双侧兔耳行塑形固定后,随机取一侧耳采用微型高频针状电极刺激耳塑形区,电极刺激条带垂直于兔耳长轴,作为实验组;另一侧不接受微型针状电极刺激,作为对照组。微型针状电极刺激后即刻及4周时观察实验组兔耳皮肤反应;于电极刺激后4周拆除固定塑形装置,观察两组兔耳塑形区形态。电极刺激8周后取两组兔耳软骨标本,HE染色观察软骨细胞和基质变化,测量软骨细胞层厚度。结果 5只新西兰白兔均存活至实验完成。实验组与微型电极刺激后即刻比较,4周时皮肤已愈合。拆除固定塑形装置后即刻两组均有明显塑形效果,但24 h后对照组基本恢复原形态,而实验组保持一定塑形形态至8周。HE染色示,对照组软骨带平滑,细胞分布均匀,表皮、真皮、软骨为正常组织学表现;实验组可见软骨细胞明显增生、增大,细胞层数增厚,微型高频电极刺激针孔处尚可见局部软骨细胞损伤变性,结缔组织中有坏死细胞及炎性细胞浸润。对照组软骨细胞层厚度为(385.714±2.027)μm,实验组为(1 594.732±1.872)μm,差异有统计学意义(t=–759.059,P=0.000)。结论微型高频针状电极刺激可有效对兔耳软骨进行重塑形,在塑形过程中软骨细胞增殖,基质也发生变化。     

红黄洗液预防留置针输注甘露醇致静脉损伤的实验研究

目的探讨红黄洗液外用预防留置针输注甘露醇所致外周静脉损伤的效果。方法将30只新西兰白兔随机分为A、B两组各15只,取其双侧耳缘静脉置入留置针。A组左耳(红黄洗液组)注射常温(20℃)20%甘露醇,同时涂搽红黄洗液;右耳(乙醇组)涂搽75%乙醇。B组左耳(加温组)静脉注射加温至35℃20%甘露醇;右耳(对照组)静脉注射常温20%甘露醇。均为2次/d,间隔6h,连续5d。实验期间肉眼观察静脉炎发生情况,实验结束后行病理组织学分析。结果肉眼观察红黄洗液组静脉损伤评分显著低于另三组(均P0.05)。病理分析,针体段炎细胞浸润、纤维组织增生四组比较,差异有统计学意义(均P0.05);针体前段血管壁损伤、炎细胞浸润、纤维组织增生及血栓形成四组比较,差异有统计学意义(P0.05,P0.01)。结论采用留置针静脉注射20%甘露醇对兔耳缘静脉有不同程度的损伤,以针体前段更甚,用红黄洗液涂搽局部预防效果优于涂搽75%乙醇及液体加温法。     

参麦注射液对兔多脏器损伤的保护作用

目的 研究麦注射液对兔多脏器损伤动物模型的保护作用。方法 大耳家兔20只，随机分为对照组和治疗组，每组10只。对照组给每只家兔一次性耳缘静脉注射阿霉素10mg，以后隔日皮下注射间羟胺10mg，4周后即制成多脏器损伤动物模型。治疗组在对照组的基础上，每次注射阿霉素和间羟胺前，经耳缘静脉注射参麦注射液，每次10ml／kg。4周后剖杀取心、肝、肺、肾行病理组织学观察。结果 对照组兔心、肝、肺、肾细胞肿胀坏死，正常结构消失，间质炎性改变及局灶性水肿和硬化，有炎性细胞浸润和血栓形成。治疗组兔心、肝、肺、肾细胞肿胀、坏死明显减轻，间质炎性细胞明显减少，局灶性硬化明显减轻。结论参麦注射液对兔多脏器损伤有明显的保护作用。     

一种增生性瘢痕动物模型的建立

目的　建立兔耳瘢痕动物模型 ,观察兔耳腹侧创面在伤后不同时间瘢痕增生的情况。方法　于 32只新西兰白兔的 6 0只兔耳腹面手术切除 2cm× 5cm全层皮肤 ,创面用 1%磺胺嘧啶银冷霜外敷包扎至愈合 ,换药 1次 /周。未作手术的 4只兔耳作对照。 (1)术后连续 12个月观察兔耳创面自然愈合情况。 (2 )用光镜、透射电镜观察兔耳创面瘢痕增生情况。 (3)用计算机图像分析系统测定 1～ 6个月的瘢痕指数。　结果　兔耳创面上皮化后其色泽、厚度和质地均经历从瘢痕形成、成熟到退化的演变过程 ;1～ 2个月的瘢痕指数 2 .2 9± 0 .74较 3～ 4个月 (2 .82± 0 .36 )和 5～ 6个月 (2 .90± 0 .84 )低 (P <0.0 5),其变化与瘢痕增生程度的消长趋势吻合。　结论　兔耳腹面全层皮肤缺损经自然愈合后形成的增生性瘢痕与人体增生性瘢痕相似 ,该模型是研究增生性瘢痕的发生机制及评估其治疗方法的较好的动物模型之一     

Effect of caffeine on erectile function via up-regulating cavernous cyclic guanosine monophosphate in diabetic rats

Erectile dysfunction (ED) is a common complication of diabetes mellitus. Phosphodiesterase-5 (PDE5) inhibitors, which inhibit the breakdown of intracellular cyclic guanosine monophosphate (cGMP), are used to treat diabetic ED. Caffeine, a nonselective PDE inhibitor used in our daily diet, is controversial regarding its effect on erectile function. To investigate the effect of caffeine on erectile function in diabetic rat models and explore the mechanism, male Sprague-Dawley rats were injected with streptozotocin to induce diabetes mellitus. The rats with blood glucose levels above 300 mg/dL were selected for the study. The rats were divided into 4 groups: group A (normal control rats), group B (diabetic rats treated with normal saline), group C (diabetic rats treated with caffeine, 10 mg/kg per day), and group D (diabetic rats treated with caffeine, 20 mg/kg per day). After 8 weeks of treatment, intracavernous pressure (ICP) was measured to assess erectile function. The radioimmunoassay was used to evaluate the level of cGMP in the cavernosum. The ICP and the cavernous cGMP decreased significantly in the diabetic rats compared with normal controls. An 8-week administration of caffeine at the given dosages increased the ICP and cavernous cGMP in diabetic rats. Caffeine consumption improved the erectile function of diabetic rats by up-regulating cavernous cGMP.     

Improvement in erectile dysfunction after neurotrophic factor gene therapy in diabetic rats

PURPOSE: Erectile dysfunction (ED) is a common but difficult to treat complication of diabetes mellitus (DM). We have previously reported herpes simplex virus (HSV) vector mediated delivery of nerve growth factor into the bladder to treat diabetic cystopathy and neurotrophin-3 (NT3) gene transfer for pyridoxine treatment. Nerve growth factor and NT3 are neurotrophic factors that may protect nerves from mechanical and metabolic damage. We investigated the effects of HSV mediated delivery of NT3 for the treatment of diabetic ED. MATERIALS AND METHODS: Male Sprague-Dawley rats weighing 300 to 400 gm were injected with 65 mg/kg streptozotocin to induce DM. After 4 weeks 20 microl containing 5 x 10 pfu replication defective HSV vector expressing lacZ (6 rats) or NT3 (6) were injected directly into the cavernous nerve sheath with a 30 gauge needle. Four weeks later the animals underwent measurement of intracavernous pressure under electrical stimulation (20 Hz, 0.5 millisecond and 10 V) of the cavernous nerve. Staining for lacZ and neuronal nitric oxide synthase in the major pelvic ganglia was also performed. RESULTS: beta-Galactosidase staining revealed lacZ positive neurons in the major pelvic ganglia. Maximal intracavernous pressure induced by electrical stimulation showed statistically significant mean values +/- SEM of 15.1 +/- 2.1 and 43.8 +/- 11.1 cm H2O in the lacZ and NT3 vector injected groups, respectively (p = 0.03). The mean number of neuronal nitric oxide synthase positive neurons per section in the NT3 group was significantly higher than that in the lacZ control group at 3.33 +/- 0.23 and 0.64 +/- 0.14 neurons per high power field, respectively (p < 0.001). CONCLUSIONS: We report that gene therapy for the treatment of diabetic ED is feasible with HSV vectors. NT3 gene therapy may be applicable for the treatment of ED induced by DM.     

The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats

The aim of this study was to assess the effect of phosphodiesterase 5 inhibitor, DA-8159, on erectile function throughout the quantitative analysis of vascular endothelial cell, smooth muscle (SM), TGF-beta1 expression in rat corpus cavernosum and measurement of intracavernous pressure (ICP) in diabetic rats. DA-8159 (0, 5, 10, 20 mg/kg) was administered orally once a day to diabetic rats. After 8 weeks, immunohistochemistry and computerized image analysis were performed to quantify the percent area within the Corpora Cavernosa occupied by the endothelial cells, SM cells and fibrotic tissues. ICP/mean arterial pressure (MAP) was also measured by electrostimulation of the cavernous nerve. Diabetic rats showed a significant decrease in the SM and endothelial cell content, and an increase in the TGF-beta1 expression level within the cavernosa areas compared to the normal rats. The mean cavernous SM, endothelial cell content and TGF-beta1 expression level were 9.7+/-0.7, 4.5+/-0.7 and 17.9+/-2.1%, respectively. DA-8159 prevented reduction of SM (12.3+/-0.4% (5 mg/kg), 13.8+/-0.4% (20 mg/kg)) and endothelial cell content (5.6+/-0.5% (5 mg/kg), 6.3+/-0.6% (20 mg/kg)). Immunoreactivity of TGF-beta1 and intracorporal fibrosis were also significantly lower in DA-8159-treated groups (11.8+/-1.2% (5 mg/kg), 9.5+/-1.1% (20 mg/kg)). Electrostimulation of the cavernous nerve induced significant increase in maximum ICP (62.2+/-13.6 mmHg in 10 mg/kg vs 37.5+/-17.5 mmHg in diabetic group) and area under the curve of the ratio of ICP/MAP (8891.09+/-1957 in 10 mg/kg vs 6315.87+/-2272 in diabetic group). These results suggest that subchronic treatment of DA-8159 can prevent the development of erectile dysfunction (ED), and provides a rationale for the use of DA-8159 as treatment of diabetic ED.     

无创性动态阴茎海绵体测压诊断阴茎勃起功能障碍

目的　探讨应用无创性动态阴茎海绵体测压 (VISER)在勃起功能障碍 (ED)诊断中的价值。　方法　对 5 3例ED患者的PGE1阴茎海绵体内注射试验、VISER及彩色双功能超声检查结果进行对比分析。　结果　PorstⅢ级者 4 3例 ,平均海绵体压力和压力指数分别为 14 4 .2 9mmHg(1mmHg=0 .133kPa)和 1.2 4。 4 2例血管功能正常 ,1例为静脉性ED ;PorstⅡ级者 10例 ,平均海绵体压力和压力指数为 87.76mmHg和 0 .81,两组间比较差别有显著性意义 (P <0 .0 5 ) ;PorstⅡ级者中动脉性ED2例 ,静脉性ED8例 ,两组间海绵体压力比较差别有显著性意义 (P <0 .0 5 )。　结论　VIS ER是一种有效的无创性诊断ED的方法 ,对动脉性及静脉性ED的鉴别亦有一定价值。     

Valsartan treatment reverses erectile dysfunction in diabetic rats

In order to investigate the effect of angiotensin receptor blockage (ARB) for the treatment on diabetic erectile dysfunction (ED), we used male Sprague-Dawley rats injected with 65 mg/kg streptozotocin to induce diabetes mellitus. The diabetic rats with ED were selected by hypodermic injection of apomorphine (APO) after 8 weeks of model setting. All rats were divided into four groups: G1 (normal control rats), G2 (diabetic rats treated with normal saline), G3 (diabetic rats treated with valsartan) and G4 (diabetic rats treated with spironolactone). After treatment with drugs for 8 weeks, the rate of erection for each group was evaluated after the injection of APO. The intracavernous pressure (ICP) of each rat was then recorded before and after the electrostimulation of the major pelvic ganglion. The rates of erection and the ICP after electrostimulation for diabetic rats treated with valsartan were significantly higher than that in diabetic rats treated with normal saline and spironolactone. The ARB may be an effective therapy for diabetics with ED.     

Gene therapy with an erythropoietin enhancer-mediated, hypoxia-inducible gene expression system in the corpus cavernosum of mice with high-cholesterol diet-induced erectile dysfunction

Cavernous hypoxia is an important factor in the pathogenesis of vasculogenic erectile dysfunction (ED). Therefore, the hypoxia-inducible gene expression system can be exploited as gene therapy for vasculogenic ED. This study was undertaken to examine the effectiveness of a hypoxia-inducible gene expression system, namely, the RTP801 promoter or the erythropoietin enhancer, in a mouse model of hypercholesterolemic ED in vivo and in primary cultured mouse cavernous endothelial cells in vitro. Two-month-old male C57BL/6micewere fed a diet containing 4% cholesterol and 1% cholic acid, and age-matched control animals were fed a normal diet for 3 months. Mouse cavernous endothelial cells were isolated and cultured under normoxic or hypoxic conditions. After treatment of animals or endothelial cells with pSV-Luc, pRTP801-Luc, or pEpo-SV-Luc vector, gene expression was evaluated by luciferase assay, and the gene expression area was evaluated by immunohistochemistry. Plasmids pRTP801-Luc and pEpo-SV-Luc induced gene expression significantly in the hypercholesterolemic mice and in cavernous endothelial cells under hypoxia, and the highest gene expression was noted in the group treated with pEpo-SV-Luc. Gene expression was higher for more than 7 days in the hypercholesterolemic mice injected with pEpo-SV-Luc than in mice injected with pSV-Luc. As shown by immunohistochemistry, the gene expression area was also greater in the pEpo-SV-Luc group than in the pSV-Luc group, but the difference was not as great as that in luciferase activity. The hypoxia-specific gene expression system could be a valuable tool for facilitating gene delivery into ischemic corpus cavernosum tissue resulting from vascular causes.     

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.     

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.     

Butea superba (Roxb.) improves penile erection in diabetic rats

The objective of the present study was to investigate the effect of ethanolic extract of Butea superba (Roxb.) on erectile dysfunction in diabetic rats by the measurement of intracavernous pressure (ICP) and on cavernosal smooth muscle relaxation. Male Sprague-Dawley rats were induced to become diabetic by a single intravenous injection of Streptozotocin (55 mg kg(-1) body weight). The ethanolic extract at the concentration of 1, 10 and 100 mg kg(-1) BW was administered orally once a day to diabetic rats in each group for 4 weeks. Diabetic rats showed a significant decrease in both ICP and the relaxation of the cavernosal smooth muscle compared with the normal rats. The extract of B. superba significantly increased the ICP with the effective dose of 10 mg kg(-1) BW (61.00 ± 11.11 mmHg versus 39.61 ± 11.01 mmHg in the diabetic control group). Moreover, the B. superba-treated group also showed enhanced relaxation of the cavernosal smooth muscle with EC(50) of 1.17 mg ml(-1). These results suggest that the extract of B. superba enhanced penile erection in diabetic rats by increasing the ICP. This might be explained by the increased blood flow as a result of the relaxation of the cavernous smooth muscle.     

Vascular endothelial growth factor (VEGF) gene therapy using a nonviral gene delivery system improves erectile function in a diabetic rat model

Erectile dysfunction (ED) is a cause of decreased quality of life in more than 70% of diabetic men. Vascular endothelial growth factor (VEGF) has shown to improve overall endothelial and smooth muscle cell dysfunction in models of ED. We describe a novel technique for nonviral, in vivo gene transfection of VEGF in the rat corpus cavernosum. Diabetic rats were transfected with DNA encoding a fusion VEGF/green fluorescent protein (GFP) complex and fluorescence microscopy was used to monitor the expression of VEGF-GFP fusion protein. Western blot and PCR analyses confirmed the expression of the GFP-VEGF fusion protein and mRNA. Functional studies using cavernous nerve stimulation revealed maximal intracavernous pressures (ICPs) of 63.1 mm Hg, and 30.7 mm Hg in the normal and diabetic control groups, respectively, and 47.4 mm Hg in VEGF-GFP-transfected diabetic group. Immunohistochemical analysis of the cavernosal tissue from transfected rats showed increased smooth muscle content compared with the diabetic control group. We show for the first time in our animal model that expression of the transfected VEGF in cavernosal tissue leads to an overall improvement of maximal ICP and smooth muscle content. On the basis of these results, it is tempting to speculate that our nonviral vector system offers an excellent system for gene delivery into cavernosal tissue, and that VEGF gene therapy using this system could be useful in improving erectile function in diabetic men.