外源性hCG对先天性尿道下裂小鼠阴茎组织EGF的影响

目的:探讨外源性hCG调控先天性尿道下裂小鼠阴茎组织EGF的作用。方法:采用昆明种小鼠建立尿道下裂动物模型。选用出生3周龄的正常雄性小鼠和先天性尿道下裂雄性小鼠各10只,腹腔内注射等量生理盐水作为对照;40只尿道下裂小鼠均分为4组,腹腔内分别注射hCG50、100、150、200IU,1次/d,共7d。酶联免疫吸附法定量检测各组小鼠阴茎组织和血清中EGF的浓度。结果:先天性尿道下裂小鼠阴茎组织EGF的浓度[(47.54±18.61)pg/ml]明显低于正常组[(84.10±21.87)pg/ml](P<0.05);采用hCG外源性干预后,阴茎组织中EGF的浓度随hCG剂量的增加而升高,分别为50IU剂量组(59.57±22.16)pg/ml、100IU剂量组(57.97±9.59)pg/ml、150IU剂量组(73.02±31.35)pg/ml和200IU剂量组(92.45±35.74)pg/ml。150IU和200IU剂量组EGF的浓度与对照组小鼠差异无显著性(P>0.05)。结论:小鼠阴茎组织EGF浓度降低可能与尿道下裂的发生存在一定关系。一定剂量范围内的外源性hCG,可使先天性尿道下裂小鼠阴茎组织EGF浓度增加。     

人绒毛膜促性腺激素调控尿道下裂兔阴茎组织血管内皮生长因子的研究

目的 探讨人绒毛膜促性腺激素(HCG)调节尿道下裂兔阴茎组织中血管内皮生长因子(VEGF)的作用. 方法选用新西兰兔于孕期第19天时,非那雄胺片剂10 mg·kg-1·d-1研成细粉,加蒸馏水适量灌胃连续给药4～7 d.自然分娩后选择尿道下裂幼兔35只,分5组,每组7只,4组分别肌内注射HCG 100、200,400、600 U,1次/d,共7 d;另1组仅注射等量生理盐水.另取7只正常幼兔作为正常组.药物干预后3周,取幼兔阴茎组织,测定VEGF含量. 结果 尿道下裂幼兔HCG 100、200、400、600 U肌内注射组阴茎组织VEGF含量分别为(5.00±2.37)、(5.63±1.73)、(10.35±2.34)、(16.91±2.34)pg/ml,生理盐水组为(3.99±1.19)pg/ml;正常组为(14.82±3.32)pg/ml.正常组与尿道下裂组100、200、400 U HCG注射组间比较差异均有统计学意义(P<0.05),与600 U HCG注射组间比较差异无统计学意义(P>0.05),400 U组与100、200、600 U HCG注射组问比较差异均有统计学意义(P<0.05);100、200 U HCG注射组与生理盐水注射组比较差异无统计学意义(P>0.05). 结论 幼兔阴茎组织VEGF浓度降低与尿道下裂的发生有相关性.一定剂量的外源性HCG可刺激尿道下裂幼兔阴茎组织VEGF浓度增加.     

先天性尿道下裂和单纯性阴茎下曲患者阴茎皮肤组织中雄激素受体表达研究

目的观察先天性尿道下裂和单纯性阴茎下曲患者阴茎皮肤组织中雄激素受体(androgen receptor,AR)的表达情况,探讨其在不同程度尿道下裂和阴茎下曲中的表达特征及规律。方法以2005年8月-2007年1月行矫正术的25例先天性尿道下裂和4例单纯性阴茎下曲患者为研究对象,采集阴茎背侧包皮、尿道口腹侧皮肤和尿道板组织。尿道下裂患者年龄1岁11个月～19岁,平均3岁7个月;阴茎下曲患者年龄3岁6个月～16岁,平均7岁1个月。以18例行包皮环切术患者的正常背、腹侧包皮作为对照。免疫组织化学染色观察并检测标本AR的表达水平和分布情况,行统计学分析。结果先天性尿道下裂、单纯性阴茎下曲和正常包皮组织中均有AR表达。正常阴茎背、腹侧包皮AR表达核阳性细胞率分别为62.94%±5.40%、62.87%±5.33%;先天性尿道下裂阴茎背侧包皮、尿道口腹侧皮肤及尿道板组织分别为59.00%±3.75%、58.46%±4.14%、52.30%±3.53%,AR表达均低于正常背、腹侧包皮(P<0.05);且尿道板组织AR表达显著低于自身背、腹侧包皮皮肤(P<0.05),自身背、腹侧包皮皮肤间差异无统计学意义(P>0.05)。与正常背、腹侧包皮比较:远、中段型尿道下裂阴茎背侧包皮AR表达差异无统计学意义(P>0.05),但尿道板组织AR表达显著降低(P<0.05);近段型背侧包皮、尿道口腹侧皮肤及尿道板组织AR表达均降低(P<0.05);下曲<45°者阴茎背侧包皮、尿道口腹侧皮肤AR表达差异无统计学意义(P>0.05),下曲≥45°者比较差异均有统计学意义(P<0.05),两组尿道板组织AR表达均降低(P<0.05)。单纯性尿道下曲患者阴茎背侧包皮、尿道口腹侧皮肤及尿道板组织AR表达核阳性细胞率分别为59.69%±2.73%、55.71%±1.67%、51.92%±1.87%,与正常包皮组织比较,AR表达呈减弱趋势。结论先天性尿道下裂及单纯性阴茎下曲阴茎皮肤组织AR表达低于正常阴茎,尿道板组织AR缺陷突出。     

齐墩果酸脂质体对顺铂所致小鼠少弱精子症的保护作用研究

目的:研究齐墩果酸脂质体(OA-Lips)对顺铂所致小鼠少弱精子症的保护作用。方法:将60只ICR小鼠随机分为对照组,模型组,阳性对照组,OA-Lips低、中、高剂量组,每组各10只。OA-Lips低、中、高剂量组每天分别给予25、50和100 mg/kg OA-Lips水溶液灌胃,阳性对照组每天给予50 mg/kg维生素E水溶液灌胃。第28天,除对照组外,其余各组小鼠均给予1次10 mg/kg顺铂溶液腹腔注射,对照组小鼠则给予相同剂量生理盐水腹腔注射。给药3 d后处死小鼠并取材,检测小鼠精子浓度和运动学参数、睾丸组织经HE染色检测,酶联免疫试剂盒测定睾酮水平。结果:与模型组相比,OA-Lips高剂量组活动精子百分率以及精子浓度显著升高(P<0.05)。睾丸组织经HE染色后,相较于模型组,OA-Lips可以显著改善睾丸组织的损伤(P<0.05),对生精小管和间质细胞有一定的保护作用。随着OA-Lips的使用剂量增加,各组小鼠前向运动的精子数量逐渐升高,各剂量组小鼠精子的VCL、VSL、VAP、LIN、STR、WOB、ALH和BCF逐渐升高。OA-Lips各剂量组小鼠血清中睾...     

抗心磷脂抗体阳性复发性流产小鼠胎盘的差异蛋白组学研究

目的 探讨抗心磷脂抗体(ACA)阳性复发性流产小鼠胎盘组织中蛋白的表达谱特征并进行生物信息学分析.方法 将20只雌性BALB/c小鼠随机分为正常对照组和ACA阳性流产模型组,每组10只.模型组于第1天和第8天通过腹腔注射β2-糖蛋白Ⅰ(β2-GPI)建立ACA阳性流产模型,正常对照组于相同时间注射等体积生理盐水,腹腔注...     

腹腔镜手术时腹腔内注射哌替啶和罗哌卡因后的药物分布与临床作用

背景目前，支持腹腔内注射哌替啶或局部麻醉药以提供有效手术后镇痛的证据尚为有限。本研究的目的旨在探讨腹腔内注射哌替啶和罗哌卡因后镇痛的有效性，并测定药物的血浆浓度。本研究的无效假设为：各组患者接受腹腔镜腹部大手术后24小时内活动时疼痛程度无统计学差异。方法本研究采用随机、双盲和空白对照的方法，在2个医学中心将250例拟行腹腔镜手术的女性患者分为5组：腹腔内注射哌替啶50或100mg（M50和M100组）、罗哌卡因150mg（R150组）、哌替啶50mg复合罗哌卡因150mg（M50R150组）和哌替啶肌肉注射50mg（对照组）。所有患者均肌肉注射生理盐水或腹腔内注射生理盐水，以保证各组处理方法的一致性。在恢复期间，将疼痛作为基本的观察指标，此后还要测定药代动力学参数。结果各组患者在手术后恢复室中及离开后的活动疼痛评分均数差异无统计学意义[对照组、M50组、M100组、R150组和M50R150组分别为2．2（2．8）、2．5（3．3）、1．6（2．5）、2．6（3．2）和2．7（3．2），P=0．50]。各组问静息疼痛评分、吗啡静脉用量、恢复指标和患者满意度的差异无统计学意义。腹腔内给予哌替啶50mg后，其血浆浓度（中位数55～60ug/L）相当于肌肉注射等量哌替啶后血浆浓度的一半（中位数113ug/L）。结论与全身注射阿片类药物相比，腹腔内注射哌替啶和罗哌卡因（单独使用或联合使用）并不能更好地缓解腹腔镜手术后的疼痛或减少阿片类药物的使用量。     

计算机三维重现兔先天性尿道下裂包皮血管

目的探寻先天性尿道下裂阴茎包皮血管变异的规律，计算机重现变异血管的三维立体构像。方法新西兰兔服用非那雄胺构建尿道下裂动物模型，阴茎组织连续切片，HE染色，显微镜下数码成像生成JPG格式图像，photoshop7．0软件及3Dmax8．0软件平台重建正常及变异阴茎血管的三维立体构像。结果采用非那雄胺成功构建了尿道下裂兔模型，根据阴茎外观形念分为阴茎头型、阴茎体型和阴囊会阴型尿道下裂。计算机三维立体构像可见正常包皮血管呈单支主干型，阴茎头型及阴茎体型尿道下裂包皮血管呈双支主干型，阴囊会阴型尿道下裂包皮血管呈网状无主干型。结论非那雄胺可以构建稳定兔先天性尿道下裂模型，正常包皮与尿道下裂包皮血管分布存在差别，不同类型尿道下裂之间包皮血管立体构像不同。     

人绒毛膜促性腺激素对青春期前低促性腺激素性腺发育不良型小阴茎皮肤组织表皮生长因子及其受体的影响

目的 观察人绒毛膜促性腺激素(HCG)对青春期前低促性腺激素性腺发育不良型小阴茎皮肤组织表皮生长因子(EGF)及其受体(EGFR)的影响.方法 10例经临床确诊的青春期前低促性腺激素性腺发育不良型小阴茎患儿予以HCG治疗;10例正常儿童为正常组.分别于治疗前、治疗后3个月进行阴茎长度测量;用酶联免疫吸附试验(ELISA)定量检测阴茎皮肤组织EGF的含量;用免疫组织化学染色(SP法)检测阴茎皮肤组织EGFR的表达.结果所有患儿治疗前阴茎长度(2.44±0.24)cm较正常组(4.29±0.26)cm短(P<0.01);其阴茎皮肤组织EGF含量(43.788±15.375)ng/L较正常组(87.106±14.483)ng/L低(P<0.01);其阴茎皮肤组织EGFR的吸光度(AD)为0.224±0.047,较正常组0.264±0.046差异无统计学意义(P>0.05).经HCG治疗后其阴茎长度(3.97±0.27)cm较治疗前(2.44±0.24)cm明显增长(P<0.01);同时其阴茎皮肤组织EGF的含量(75.694±16.014)ng/L较治疗前(43.788±15.375)ng/L升高(P<0.01);其阴茎皮肤组织EGFR的AD为(0.242±0.054),较治疗前(0.224±0.047)差异无统计学意义(P>0.05).结论 青春期前低促性腺激素性腺发育不良型小阴茎组织内EGF的含量低于正常同龄期儿童;HCG治疗可促进青春期前低促性腺激素性腺发育不良型小阴茎组织EGF的含量升高,从而促进阴茎生长发育.     

泌乳素瘤性ED大鼠阴茎组织nNOS表达及超微结构变化的初步研究

目的:采用已烯雌酚(DES)诱导建立大鼠垂体泌乳素瘤勃起功能障(P-ED)模型,并研究泌乳素瘤ED大鼠阴茎n NOS表达及超微结构的变化。方法:取雄性Wistar大鼠,分为生理盐水对照组10只、花生油对照组10只及模型组20只。模型组腹腔内注射DES建立泌乳素瘤模型,8周后进行阿扑吗啡(APO)试验测定阴茎勃起功能筛选出P-ED大鼠模型。取垂体行病理学检查,并测定垂体质量、血清泌乳素(PRL)及睾酮(T)浓度。免疫组化法测定阴茎组织n NOS表达的变化,透射电镜观察阴茎海绵体组织超微结构变化。结果:APO试验共筛选出P-ED大鼠模型15只。与生理盐水及花生油对照组相比,注射DES 8周时大鼠垂体质量显著升高[(46.7±15.5)mg vs(11.7±2.4)、(12.4±2.3)mg,P均0.05)];血清PRL浓度显著升高[(1 744.9±304.5)ng/ml vs(11.5±2.4)、(10.6±1.9)ng/ml,P均0.01)];FT浓度降低[(1.54±0.46)ng/ml vs(3.11±1.08)、3.04±1.11)ng/ml,P均0.05)]。与生理盐水及花生油对照组相比,注射DES 8周时大鼠阴茎勃起次数显著减少(16.7%vs 100%、vs 87.5%,P0.05)。透射电镜下,8周时阴茎海绵体内皮细胞、平滑肌细胞等均有显著改变。与生理盐水及花生油对照组相比,P-ED组8周时阴茎组织n NOS表达平均光密度值(MOD)显著减少(0.024±0.011 vs 0.066±0.019、0.058±0.021,P均0.05)。结论:阴茎组织超微结构的变化及n NOS表达减少可能是泌乳素瘤大鼠发生ED的主要机制。     

ERβ对小鼠阴茎海绵体血管内皮保护作用的实验研究

目的:初步探讨雌激素受体β(ERβ)对小鼠阴茎血管内皮的保护作用。方法:随机选取ERβ基因敲除(ERβKO)雄性小鼠和相应野生型雄性小鼠各12只,随机分为4组:正常对照组、ERβKO组、野生型+TNFα处理组和ERβKO+TNFα处理组。ERβKO组及正常对照组腹腔注射生理盐水,野生型+TNFα处理组和ERβKO+TNFα处理组给予TNFα6μg/(kg.d)腹腔注射,连续14 d。观察阿朴吗啡诱导的自发勃起反应;制备阴茎组织切片,内皮细胞标志物CD34、vWF免疫组化染色观察海绵窦内皮细胞变化,TUNEL法检测海绵体组织细胞凋亡情况。结果:与正常对照组相比,ERβKO组勃起潜伏期延长(P<0.05),但勃起次数无显著差异;ERβKO+TNFα组与野生型+TNFα组潜伏期显著延长(P<0.05),勃起次数显著减少(P<0.05),以ERβKO+TNFα组变化更显著。免疫组化结果显示,与正常对照组(CD34:3.00±0.00,vWF:2.75±0.50)比较,海绵体组织CD34、vWF蛋白表达在ERβKO组(CD34:2.25±0.50,vWF:2.00±0.00)、ERβKO+TNFα组(CD34:0.25±0.50,vWF:0.33±0.58)、野生型+TNFα组(CD34:1.50±0.58,vWF:1.25±0.50)均显著减少(P<0.05),且ERβKO+TNFα组比野生型+TNFα组减少更显著(P<0.05)。仅在ERβKO+TNFα组海绵体发现凋亡细胞。结论:ERβ基因敲除后,尤其在内皮损伤因素TNFα作用下,小鼠阴茎血管内皮细胞减少,提示ERβ对阴茎海绵窦内皮具有保护效应。     

Chromosomal anomalies in cryptorchidism and hypospadias

PURPOSE: We studied the incidence of chromosomal anomalies in patients with cryptorchidism and hypospadias to determine the value of routine karyotyping in this population. MATERIALS AND METHODS: Blood samples from 984 patients with cryptorchidism and/or hypospadias were studied for chromosome analysis. RESULTS: Chromosomal anomalies were detected in 27 of the 916 patients (2.94%) with cryptorchidism and in 7 of the 100 (7%) with hypospadias. There were chromosomal aberrations in 13 of the 706 patients (1.84%) with isolated cryptorchidism (no additional congenital abnormalities) and in 14 of the 210 (6.67%) with cryptorchidism with associated anomalies. We identified normal karyotypes in 26 patients with isolated hypospadias, although 7 of the 74 (9.46%) with hypospadias and additional abnormalities had chromosomal aberrations. CONCLUSIONS: It is important to perform karyotyping in these patients, mainly when they show associated abnormalities other than cryptorchidism or hypospadias. However, cost-benefit analysis must be done in each case.     

Hypospadias repair: Byar's two stage operation revisited.

BACKGROUND: Hypospadias is a congenital deformity characterised by an abnormally located urethral opening, that could occur anywhere proximal to its normal location on the ventral surface of glans penis to the perineum. Many operations had been described for the management of this deformity. METHODS: One hundred and fifteen patients with hypospadias were treated at the Department of Plastic Surgery, Hospital Kuala Lumpur, Malaysia between September 1987 and December 2002, of which 100 had Byar's procedure performed on them. RESULTS: The age of the patients ranged from neonates to 26 years old. Sixty-seven patients had penoscrotal (58%), 20 had proximal penile (18%), 13 had distal penile (11%) and 15 had subcoronal hypospadias (13%). Operations performed were Byar's two-staged (100), Bracka's two-staged (11), flip-flap (2) and MAGPI operation (2). The most common complication encountered following hypospadias surgery was urethral fistula at a rate of 18%. CONCLUSIONS: There is a higher incidence of proximal hypospadias in the Malaysian community. Byar's procedure is a very versatile technique and can be used for all types of hypospadias. Fistula rate is 18% in this series.     

Dorsal tunica albuginea plication to correct congenital and acquired penile curvature: a long-term follow-up

OBJECTIVE: To evaluate the long-term efficacy of a tunica albuginea dorsal plication technique for treating congenital and acquired penile curvature. PATIENTS AND METHODS: We retrospectively evaluated 83 patients (median age 1.8 years) who had their penile curvature corrected surgically using dorsal tunica albuginea plication between 1992 and 2002. The results were evaluated objectively using a pharmacological erection test or subsequently based either on the parents' reports or patients' self-assessment. The median (range) follow-up was 6 (0.7-10) years. RESULTS: Seventy (84%) patients had penile plication as an integral part of hypospadias repair, while the remaining 13 (16%) with a normal urethra had dorsal plication only. Twenty-eight (34%) of the 83 patients had an erection test during a repeat hypospadias repair or closure of a urethrocutaneous fistula; 22 of these had a straight penis, while the remaining six required additional plication for a satisfactory cosmetic outcome. Parents of 45 (54%) children reported that their child had a normal erection with no chordee during the follow-up. Ten (12%) adult patients reported straight erections enabling satisfactory penetration and sensation during sexual intercourse. None of the patients reported penile shortening or erectile dysfunction after surgery, and none had recurrent curvature during the follow-up. There was no difference in the results between patients with congenital or acquired penile curvature. CONCLUSIONS: Dorsal plication of the tunica albuginea is a simple and effective method in the long term for correcting congenital and acquired penile curvature.     

新生儿尿道下裂I期手术修复

目的:探讨I期手术治疗新生儿尿道下裂的可行性。方法:1998年5月~2004年6月,对16例新生儿先天性尿道下裂患儿实施了尿道下裂I期修复术,患儿年龄1~29 d,平均13 d;其中尿道下裂I型4例,II型8例,III型3例,IV型1例。结果:14例痊愈,1例尿道狭窄,1例尿瘘,I期手术成功率87.5%(14/16)。结论:在确保麻醉安全的前提下,如果病例选择适当,对新生儿尿道下裂实施I期修复术是可行的。     

纵行带蒂包皮皮瓣尿道成形术一期矫治小儿尿道下裂

目的评价纵行带蒂包皮皮瓣作为尿道重建材料在修复尿道下裂的可行性及效果。方法采用纵行带蒂包皮皮瓣尿道成形术矫治先天性尿道下裂21例,其中阴茎型14例,阴囊型7例。结果20例重建尿道成活,外形接近正常。结论该术式具有并发症少,外形接近正常等优点,值得临床推广应用。     

Hypospadias: a familial study.

The families of 177 boys with varying degrees of hypospadias were evaluated prospectively to determine the occurrence of hypospadias and other congenital anomalies within this population. A significant number of male subjects in each family member category were affected, with first degree relatives (brothers and fathers) having a 14 and 9 per cent incidence, respectively. Siblings were at a greater risk for having this anomaly when the proband had a more severe degree of hypospadias and when the abnormality also was present in other relatives. A multifactorial mode of inheritance is suggested as the basis for transmission of this congenital defect.     

Gene expression profiles in mouse urethral development

OBJECTIVE: To analyse the gene expression profiles of the mouse genital tubercle (GT) during urethral tube development at embryonic (E) days E14, E15, E16 and E17, as the aetiology of hypospadias, one of the most common congenital anomalies, remains unknown. MATERIALS AND METHODS: During GT development the urethral folds fuse to form an epithelial seam; subsequently, the epithelial seam disappears, resulting in the normal tubular urethra. Abnormalities in urethral seam formation and remodelling might explain hypospadias, and elucidating the molecular developmental mechanisms underlying normal penile development might provide the basis for understanding hypospadias. Total RNA was isolated from the genital tubercle at embryonic days E14, E15, E16, and E17. Together with reference RNA, sample RNA was labelled with Cy-3 and Cy-5 respectively and hybridized to a 16 000-mouse gene array that included the Incyte GEM2.1 and NIA 7k sets. Candidate genes were analysed by immunohistochemistry and real-time polymerase chain reaction. RESULTS: Using cDNA microarrays, we identified the up-regulation of genes involved in the transforming growth factor (TGF)-beta and Wnt-Frizzled pathways, and of thrombospondin (TSP) 4, a member of a cell-migration molecule family, all candidates for involvement in urethral tube formation. Immunohistochemistry showed TGFbeta1, TGFbeta receptor III, and Frizzled1 were expressed exclusively in E14-E17 urethral epithelium. TSP4 was expressed in the mesenchymal basal layer underlying E17 GT skin epidermis. CONCLUSIONS: Many signalling pathways are involved in late GT development, and cell migration molecules might have an important role in urethral tube formation.     

先天性阴茎弯曲的手术矫治

目的:通过几种常用的手术方法来探讨先天性阴茎弯曲的治疗效果。方法:2002年3月~2005年2月共治疗先天性阴茎弯曲76例,其中合并尿道下裂67例、尿道上裂5例和尿道开口正常4例。治疗方法包括术前5周绒毛膜促性腺激素治疗、术中阴茎皮肤彻底脱套、尿道周围异常分布纤维索带完全松解、阴茎腹侧或背侧白膜折叠、白膜切开全厚游离皮瓣或睾丸鞘膜嵌入等手术。结果:术后随访2个月~2年,平均9.3个月。88%(67例)获得完全矫正;8%(6例)尚遗留轻度弯曲,暂无需再次手术,但需远期观察;另有4%(3例)虽手术中阴茎弯曲已明显纠正,但术后出现复发,需再次手术。结论:通过上述几种治疗方法,绝大多数先天性阴茎弯曲可以得到充分矫正。