疏肝理气活血法对肝郁气滞大鼠阴茎海绵体NOS活性影响的实验研究

目的 探求肝郁气滞男性阴茎海绵体组织中NOS活性及疏肝理气活血中药对其影响。方法 采用与人类精神性应激十分相似的非损伤性应激刺激法,制造肝郁气滞型大鼠动物模型,以免疫组化与计算机图象分析技术测定海绵体组织中NOS活性。结果 证明肝郁气滞动物模型组阴茎海绵体组织中nNOS活性与空白对照组有显著性差异(P<0.01),疏肝理气活血中药高剂量组阴茎海绵体组织中nNOS活性与模型组有显著性差异(P<0.05)。结论 肝郁气滞可导致阴茎海绵体组织中nNOS活性下降,而疏肝理气活血中药有增强阴茎海绵体组织中nNOS活性的作用。 这可能是形成心因性ED病理基础的一个重要环节。     

中药益坎胶囊对动脉性勃起功能障碍大鼠阴茎海绵体平滑肌细胞表型转化的影响

目的:探讨中药益坎胶囊对动脉性勃起功能障碍(ED)大鼠阴茎海绵体平滑肌细胞表型转化的影响,以揭示益坎胶囊治疗ED的机制。方法:选取SD大鼠50只,其中10只设为正常组,另40只通过结扎双髂内动脉造成动脉性ED模型。造模后将其中10只设为模型对照组,其余30只灌胃给予ED治疗中药益坎胶囊,浓度分别为1.88、0.94、0.47 g/kg。给药1个月后,经腹腔注射阿朴吗啡,观察大鼠呵欠次数和阴茎勃起次数;切取大鼠的阴茎组织标本,通过免疫组化法观测海绵体平滑肌细胞收缩型性标志物碱性调宁蛋白(calponin 1)和合成型标志物骨桥蛋白(OPN)的表达,实验组结果与正常组和对照组进行比较。结果:注射阿朴吗啡后,正常组大鼠勃起次数为(4.48±1.25)次,模型对照组为(1.63±0.22)次,两组比较,差异有统计学意义(P0.01);给药后,中药益坎胶囊高、中、低剂量组大鼠勃起次数有明显改善[高剂量:(3.05±1.37)次;中剂量:(2.98±0.16)次;低剂量:(1.75±0.40)次]。免疫组化结果显示,模型对照组大鼠海绵体平滑肌细胞calponin 1表达减少,而OPN表达增多,与正常组相比差异有统计学意义(P0.05);与模型对照组相比,给药后,中药益坎胶囊高、中、低剂量组大鼠海绵体平滑肌细胞calponin 1表达增多,OPN表达减少。结论:中药益坎胶囊能改善动脉性ED大鼠的勃起功能,抑制海绵体平滑肌细胞表型由收缩型向合成型转化。     

不同剂量香烟烟雾提取物对阴茎海绵体NOS活性和Cx43蛋白的影响

目的:探讨不同剂量的香烟烟雾提取物对雄性大鼠勃起功能的影响,进一步研究吸烟导致ED的发病机制。方法:75只健康雄性SD大鼠(8周龄),随机分为5组(15只/组)。A组为对照组;B组为皮下注射二甲基亚砜(DMSO)组;C组为皮下注射香烟烟雾提取物(CSE)低剂量组;D组为皮下注射CSE中剂量组;E组为皮下注射CSE高剂量组。应用SD雄性大鼠建立皮下注射CSE模型60 d后,经皮下注射阿朴吗啡(APO)后观察大鼠阴茎勃起情况,处死大鼠取阴茎海绵体组织。一部分标本采用激光共聚焦扫描显微镜方法检测缝隙连接蛋白43(Cx43)的表达;另一部分标本采用比色法测定大鼠阴茎海绵体组织中NOS活性。结果:不同剂量CSE组阴茎勃起次数、阴茎海绵体组织NOS活性和海绵体平滑肌中Cx43表达与DMSO组和对照组比较均明显减少(P<0.05)。实验组中,阴茎勃起次数、阴茎海绵体组织NOS活性和Cx43表达均随着CSE剂量的增加而减少。DMSO组与对照组比较差异无统计学意义(P>0.05)。结论:CSE使阴茎海绵体组织NOS活性明显降低、海绵体平滑肌中Cx43蛋白表达明显减少并且严重影响阴茎勃起功能,并且CSE剂量越大,其影响越明显。提示,Cx43蛋白表达下调、NOS活性降低可能是CSE导致ED的发病机制之一。     

晚期糖基化终产物及其受体对大鼠阴茎海绵体组织中内皮素-1活性的影响

目的:通过观察大鼠阴茎海绵体组织中晚期糖基化终产物(AGEs)及其受体(RAGE)的变化对内皮素1(ET-1)活性的影响,探讨AGEs在糖尿病性勃起功能障碍(DMED)发生发展中的作用。方法:成年雄性SD大鼠60只,随机取40只用于制作糖尿病模型,造模后共27只大鼠成模,将其分为两组:糖尿病(DM)组15只和糖尿病+氨基胍给药(DM+AG)组12只;另20只大鼠平分为两组:正常对照(NC)组和正常对照+氨基胍给药(NC+AG)组;两组氨基胍(AG)给药组大鼠造模后即在其饮水中按1g/L剂量加入AG。饲养8周后取各组大鼠阴茎海绵体组织,一部分用于免疫组化法观察分析AGEs及其受体的分布和表达,剩余部分匀浆后检测AGE-肽(AGE-P)含量和ET-1活性。结果:DM组阴茎海绵体组织中AGEs和RAGE的表达、AGE-P含量及ET-1活性明显高于正常对照组(P<0.05);正常对照组与NC+AG组间比较在各项指标上则无明显差异(P>0.05)。结论:糖尿病状态下AGEs与RAGE的结合效应可以引起大鼠阴茎海绵体组织中ET-1活性的增强,从而促进DMED的发生发展。     

安雄对去势大鼠离体阴茎海绵体平滑肌舒张性的影响

目的 :探讨口服雄激素类药安雄对大鼠阴茎海绵体平滑肌舒张性的调节作用。　方法 :去势大鼠分别给予高、低剂量的安雄 ,与假手术组、去势组大鼠进行对照观察。治疗 4周后分别切取其阴茎海绵体 ,制成海绵体肌条 ,应用去甲肾上腺素对海绵体肌条进行预收缩 ,继予硝普钠 (SNP)、电刺激 (EFS)观测海绵体平滑肌的舒张性 ,比较各组的舒张百分率。　结果 :高剂量安雄 (2 0mg/kg)组其离体平滑肌条 ,对 10 -3 mol/LSNP和EFS的舒张百分率高于去势组 ;低剂量组 (10mg/kg)对 10 -3 mol/LSNP诱导的舒张百分率也高于去势组。统计学处理差异有显著性 (P <0 .0 1) ,　结论 :去势大鼠应用安雄可提高离体大鼠海绵体平滑肌的舒张百分率 ,可增强其海绵体平滑肌的舒张性     

晚期糖基化终产物及其受体对大鼠阴茎海绵体组织中内皮素-1活性的影响

目的：通过观察大鼠阴茎海绵体组织中晚期糖基化终产物（AGEs）及其受体（RAGE）的变化对内皮素1（ET-1）活性的影响，探讨AGEs在糖尿病性勃起功能障碍（DMED）发生发展中的作用。方法：成年雄性SD大鼠60只，随机取40只用于制作糖尿病模型，造模后共27只大鼠成模，将其分为两组：糖尿病（DM）组15只和糖尿病＋氨基胍给药（DM＋AG）组12只；另20只大鼠平分为两组：正常对照（NC）组和正常对照＋氨基胍给药（NC＋AG）组；两组氨基胍（AG）给药组大鼠造模后即在其饮水中按1g／L剂量加入AG。饲养8周后取各组大鼠阴茎海绵体组织，一部分用于免疫组化法观察分析AGEs及其受体的分布和表达，剩余部分匀浆后检测AGE-肽（AGE-P）含量和ET-1活性。结果：DM组阴茎海绵体组织中AGEs和RAGE的表达、AGE-P含量及ET-1活性明显高于正常对照组（P〈0．05）；正常对照组与NC＋AG组间比较在各项指标上则无明显差异（P〉0．05）。结论：糖尿病状态下AGEs与RAGE的结合效应可以引起大鼠阴茎海绵体组织中ET-1活性的增强，从而促进DMED的发生发展。     

小檗碱对大鼠阴茎海绵体磷酸二酯酶5mRNA水平的影响

目的 :检测大鼠阴茎海绵体中磷酸二酯酶 5 (PDE5 )mRNA的表达 ,进而探讨小檗碱 (berberine ,Ber)的分子作用机制。　方法 :通过逆转录酶链反应 (RT PCR)技术检测大鼠阴茎海绵体中PDE5mRNA的表达。　结果 :大鼠阴茎海绵体中有PDE5A1和PDE5A2mRNA的表达 ,以PDE5A2为主要的异构酶。与内参照 β 肌动蛋白相比 ,对照组、Ber孵育 1和 3h组的PDE5A1及PDE5A2基因mRNA的相对表达量分别为 :0 .2 2± 0 .0 2 ,0 .4 1± 0 .0 1 ;0 .1 5± 0 .0 1 ,0 .34± 0 .0 2 ;0 .1 0± 0 .0 1 ,0 .1 2± 0 .0 1。与对照组相比 ,PDE5A1、PDE5A2的mRNA表达 ,在Ber孵育 1h组降低了 32 %和 1 7%,3h组降低了 5 5 %和 71 %,其中尤以应用Ber 3h后PDE5A2的mRNA减少最为明显 (n =5 ,P <0 .0 1 )。　结论 :Ber对NO cGMP信号通路的下游关键酶 (PDE5 )具有一定的调控作用 ,尤其是抑制PDE5A2的mRNA表达 ,为Ber治疗勃起功能障碍的分子机制之一。     

晚期糖基化终产物及其受体对大鼠阴茎海绵体组织中氧自由基代谢的影响

目的 通过观察大鼠阴茎海绵体组织中晚期糖基化终产物（AGEs）及其受体（RAGE）的变化对氧自由基代谢的影响，探讨AGEs在糖尿病性勃起功能障碍（DMED）发生发展中的作用。方法 成年雄性SD大鼠60只，随机取40只用于制作糖尿病模型，造模成功的大鼠分为两组：糖尿病（DM）组和糖尿病＋氨基胍给药（DM＋AG）组；另20只大鼠亦分为两组：正常对照（CO）组和正常对照＋氨基胍给药（CO＋AG）组；氨基胍（AG）给药组大鼠造模后即在其饮水中按1g／L剂量加入AG。饲养8周后取各组大鼠阴茎海绵体组织，一小段用于免疫组化观察分析AGEs及其受体的分布和表达，剩余部分匀浆后检测AGE-肽（AGE—P）含量、丙-醛（MDA）含量及超氧化物歧化酶（SOD）活性。结果 DM组阴茎海绵体组织中AGEs和RAGE的表达、AGE—P含量及MDA含量明显高于CO组（P〈0．05），而SOD活性则明显低于后者（P〈0．05），而AG则明显减少了DM大鼠阴茎海绵体组织中AGEs和RAGE表达、AGE—P及MDA的生成，增强了SOD活性；CO组与CO＋AG组间比较在各项指标上则无明显差异（P〉0．05）。结论 糖尿病状态下AGEs与RAGE的结合效应可以引起大鼠阴茎海绵体组织中氧自由基的产生增多，抗氧化能力的下降，从而促进DMED的发生发展。     

反义寡脱氧核苷酸对人阴茎海绵体平滑肌细胞PDE5的抑制作用

目的　观察反义寡脱氧核苷酸对人阴茎海绵体平滑肌细胞 5型磷酸二酯酶 (PDE5 )的抑制作用 ,为阴茎勃起功能障碍的基因治疗提供理论和实验依据。　方法　将PDE5基因反义寡脱氧核苷酸与DOTAP转染人阴茎海绵体平滑肌原代细胞 ,Western印迹法检测转染后不同时间 (1～ 4 8h)海绵体平滑肌细胞内PDE5的浓度变化 ,观察反义寡脱氧核苷酸对平滑肌细胞内PDE5的作用。　结果　转染后 1～ 6h ,反义组人阴茎海绵体平滑肌原代细胞内PDE5表达量较对照组显著降低 (P=0 .0 0 0～ 0 .0 14 ) ;转染后 12～ 4 8h ,三组细胞内PDE5的表达比较 ,差别无显著性意义 (P =0 .189～0 .96 2 )。　结论　PDE5基因反义寡脱氧核苷酸对人阴茎海绵体平滑肌细胞PDE5有抑制作用。     

红景Ⅰ号方对双侧海绵体神经损伤SD大鼠阴茎组织中缝隙连接蛋白43表达的影响

目的:探索红景Ⅰ号方对双侧海绵体神经损伤大鼠勃起功能及其阴茎组织中缝隙连接蛋白43的干预作用. 方法:将50只SD大鼠随机均分为5组,分别为假手术组、双侧海绵体神经损伤组、红景Ⅰ号方低、中、高剂量组.利用止血钳钳夹大鼠双侧海绵体神经以造成损伤,红景Ⅰ号方组给予不同剂量(2.835、5.67、11.34g/kg)灌胃.2...     

A novel compound JPM8: in vivo penile activity promotion in rats,effect on the relaxation and cGMP/cAMP accumulation in isolated rabbit corpora cavernosa

JPM8 is a novel sildenafil-like PDE5 inhibitor. Its efficacy was tested in vivo by the oral administration of drugs to a rat model and recording penile activity changes. Effect on the relaxation of the rabbit cavernosa was tested in vitro using an organ bath were drugs are added to the tissue media and relaxation was recorded using a transducer connected to a chart recorder. The accumulation of cGMP and cAMP was measured by incubation of cavernosa strips and then extracting the produced cGMP and cAMP in the incubation mixture, then quantitating it using ELISA. JPM8 showed increased and promoted sexual and penile activity in rats in a similar but slightly higher trend than the positive control sildenafil. JPM8 was more efficient in relaxing the rabbit corpora cavernosa than sildenafil. The cGMP and cAMP accumulation showed a similar trend for both drugs. We concluded that JPM8 was very effective in promoting sexual activity in rats, relaxing the corpora cavernosa and promoting cGMP accumulation in rabbits.     

Medikamentöse Therapie des benignen Prostatasyndroms mit Phosphodiesterase-5-Inhibitoren

Phosphodiesterase-5 (PDE5) inhibitors, such as sildenafil, tadalafil and vardenafil are first line treatment for erectile dysfunction (ED). These PDE5 inhibitors are known to increase cyclic guanosine monophosphate (cGMP) concentrations in the smooth muscle cells of the corpora cavernosa penis by inhibiting PDE5, leading to smooth muscle relaxation. This mode of action is also believed to result in prostatic smooth muscle relaxation and to improve lower urinary tract symptoms (LUTS). Randomized controlled trials have shown beneficial effects on LUTS and on objective parameters such as maximum urinary flow rate (tadalafil). Based on these data tadalafil was recently approved for treatment of patients with male LUTS; however, the mechanisms leading to improvement of symptoms are still under debate.     

去氧肾上腺素治疗TURP术中阴茎勃起 (附14例报告)

目的 总结阴茎海绵体内注射去氧肾上腺素治疗阴茎勃起的临床体会，探讨其安全性及临床效果。方法 阴茎海绵体内注射去氧肾上腺素，总结起效时间、剂量、并发症的发生情况。结果所有14例患者，在2-5min内勃起消失，手术继续进行。注射前后平均动脉压及心率变化无显著差异（P〉0．05）。无并发症。结论 阴茎海绵体内注射去氧肾上腺素是治疗TURP术中阴茎勃起的安全、有效的方法。     

B超下阴茎海绵体"繁星征"与 ED

目的 探讨B超下阴茎海绵体出现的“繁星征”与ED的关系,研究其发病机制。方法 30例ED患者行阴茎海绵体B超检查,并与30例无ED志愿者行B超对照。另对l例ED“繁星征”患者行阴茎海绵体病理检查。结果 30例ED患者中,29例发现有B超下阴茎海绵体“繁星征”。其中26例全阴茎弥散分布强回声光点,为临床诊断的中、重度ED患者（IIEF-5评分〈11分）。另3例仅局限在一部分,且回声光点较少,为轻度ED（IIEF-5评分12～19分）。而无ED志愿者无此现象。1例“繁星征”患者病理检查为阴茎海绵体胶原纤维增生伴玻璃样变。结论 阴茎海绵体广泛纤维化是出现B超下“繁星征”的病理基础。因限制海绵窦充盈而影响阴茎勃起。外伤与炎症是其致病因素。     

海绵体神经在前列腺尖部及远端的行程与分布

目的 观察海绵体神经在前列腺尖部及其远端的行程和分布,探讨海绵体神经与周围 组织的关系.方法 3具成年男性尸体尿道和阴茎标本,自前列腺尖部至阴茎头连续切片行HE染色和神经纤维嗜银染色,观察海绵体神经在前列腺尖部及其远端尿道膜部阴茎的行程与分布.结果 海绵体神经纤维束行于前列腺尖部和尿道膜部约3点到9点处,距离尿道腔约3～5 mm,向远端进入阴茎海绵体近段.自尿道膜部向前走行与海绵体静脉丛并行进入海绵体中隔.结论 海绵体神经在前列腺尖部以及阴茎近段与尿道及海绵体静脉关系密切,该部位尿道和海绵体静脉相关手术容易损伤海绵体神经.     

Anatomic study of arterial and venous cavernospongious shunt in the human penis: surgical findings

The vascularization of the penis corpora cavernosa and the corpus spongiosum of foetus, children and adults was studied via intra-vascular injection with gelatenous india ink. The microscopic vision of sagittal and transvers sections of the penis showed perforate deep arterial system of the cavernosa directly anastomosed the urethral submucosal arteries in order to establish the shunt between the corpora cavernous arteries and spongious arterial network. Those vascular connection systems of the penis provided well diffusion of the drugs.     

Spongiosolysis: a new surgical treatment of impotence caused by distal venous leakage

Until recently ligation of the dorsal veins of the penis had been the only effective surgical treatment in cases of erectile dysfunction caused by venous insufficiency of the corpora cavernosa. Failure of this operation can be owing to persistent distal venous leakage consisting of venous shunts between the distal corpora cavernosa and corpus spongiosum, which can be demonstrated by cavernosography. These shunts can be closed successfully by spongiosolysis, that is by dissecting the distal half of the corpus spongiosum and by isolating the tips of the corpora cavernosa. Of 5 patients who underwent spongiosolysis after previous ligation of the dorsal vein of the penis 4 regained erectile ability with the help of intracavernous injection of a vasoactive drug mixture (15 mg. per ml. papaverine hydrochloride plus 0.5 mg. per ml. phentolamine mesylate, 0.5 to 2 ml. per injection), which was necessary because of concomitant arterial lesions demonstrated by arteriography. The only failure proved to be persistent venous insufficiency of the deep dorsal vein of the penis. Since none of the patients had any serious complication spongiosolysis seems to be a safe procedure in the treatment of distal venous leakage.     

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.