豚鼠逼尿肌不稳定模型的建立与评估方法的改进

目的寻找一种简单、可靠的方法建立并评估豚鼠膀胱逼尿肌不稳定模型。方法成年雌性豚鼠经会阴部尿道结扎，6周后行膀胱穿刺充盈性膀胱测压，观察膀胱压力、容量变化及逼尿肌不稳定的发生情况。结果实验组逼尿肌不稳定发生率35．9％，对照组无发生，其中逼尿肌不稳定膀胱组膀胱最大压力和最大容量较对照组显著增加（P〈0．01）。结论经会阴部尿道结扎、膀胱穿刺充盈性膀胱测压是建立及评估豚鼠膀胱出口梗阻引起逼尿肌不稳定模型的一种简单、可靠的方法。     

膀胱出口梗阻大鼠膀胱过度活动的研究

目的:建立膀胱出口梗阻大鼠模型,诱发逼尿肌不稳定(DI),研究膀胱出口梗阻伴发膀胱过度活动的病理生理学特征。方法:选择38只成年SD雌性大鼠,随机分为模型组和对照组,结扎膀胱颈部建立膀胱出口梗阻模型。建模后3、6、9、12周采用BL-410生物机能实验系统测定膀胱压,以充盈期出现DI作为膀胱过度活动存在的标准,记录并计算DI阳性率和频率、最大排尿压(MVP)、最大膀胱容量(MCC)、膀胱顺应性(BC)和剩余尿量(PVR)。用光镜观察建模不同时期膀胱组织的病理学改变。结果:模型组大鼠3、6、9、12周DI阳性率分别为37.50%、75.00%、75.00%、62.50%。MVP、MCC、BC、PVR和DI频率较对照组增高(P<0.01),第9周大鼠PVR、MVP、MCC高于第3、6和12周。不同时期病理学改变呈现出膀胱容量增加、肌层逐渐增厚和纤维化的过程。结论:膀胱出口梗阻与逼尿肌不稳定的发生具有潜在的相关性,其病理学改变和尿流动力学参数反映了膀胱的病理生理学特点。     

尿道外口皮下注射透明质酸建立大鼠膀胱出口梗阻模型及效果评价

目的 通过尿道外口皮下注射透明质酸的方法建立一种简单微创、重复性好的大鼠膀胱出口梗阻(BOO)动物模型,并与传统开放手术BOO动物模型进行比较,评估其梗阻效果及并发症情况.方法 共40只成年雌性SD大鼠进行试验,随机分为3组,即尿道外口透明质酸注射组(简称注射组)、开放手术近端尿道结扎组(简称手术组)和对照组.注射组(n=15)采用0.2 mL透明质酸在尿道外口皮下周围注射的方法建立模型;手术组(n=15)利用传统开放性近端尿道结扎的方法建立模型;另10只正常大鼠作为对照.4周后检测各组充盈性膀胱测压检测梗阻效果、术后并发症、膀胱重量、以及HE染色检测膀胱组织学改变.结果 注射组较手术组的模型操作时间显著缩短(P＜0.05),无切口感染和膀胱结石等并发症;充盈性膀胱测压结果提示:与对照组相比,注射组和手术组均检测到膀胱容量、排尿频率和残余尿量增加及储尿末期逼尿肌不稳定收缩的典型膀胱出口梗阻的尿动力学表现;注射组和手术组膀胱重量明显增加(P＜0.05),HE染色可见梗阻后膀胱黏膜下及间质明显水肿、肌层厚度均显著高于对照组(P＜0.05).结论 大鼠尿道外口透明质酸注射简单微创、并发症少、效果明确、可重复性好,是一种有效的膀胱出口梗阻动物模型.     

糖尿病对膀胱逼尿肌兴奋性、收缩性及顺应性影响的实验研究

目的:探讨糖尿病(DM)对膀胱逼尿肌兴奋性、收缩性、顺应性的影响及糖尿病神经源性膀胱尿道功能障碍(NVUDD)的发病机制.方法:建立SD大鼠DM动物模型,于10周后行充盈性膀胱测压及离体逼尿肌条机械牵拉、电及胆碱类药物刺激试验.结果:DM动物模型10周后不稳定膀胱(DI)的发生率为64.7%,逼尿肌顺应性升高;DI组、DM后稳定组与正常对照组相比,牵拉逼尿肌致其出现收缩时的张力明显降低,电刺激产生的收缩力明显减弱;DI组逼尿肌胆碱类药物产生的收缩力明显减弱.结论:DM后NVUDD的发生率较高,其逼尿肌的收缩功能受损较重,DNBUD的发生与逼尿肌自身的神经源及肌源性改变密切相关.     

肾上腺素β3受体与梗阻后逼尿肌不稳定关系的实验研究

目的　探讨肾上腺素β3 受体 (β3 AR)在膀胱出口梗阻 (BOO)型逼尿肌不稳定 (DI)中的作用。　方法　Wister大鼠 15只 ,建立BOO后DI模型 ,6周后行充盈性膀胱测压 ,根据是否有DI将下尿路梗阻大鼠分为DI组和逼尿肌稳定 (DS)组 ,正常大鼠 8只作为对照组。用离体逼尿肌条拉力实验观察BRL37344A(β3 AR激动剂 )对逼尿肌自律性和舒张功能的影响 ,RT PCR检测膀胱 β3 ARmRNA含量。　结果　BOO后DI发生率为 6 7% (10 / 15 )。BRL37344A能明显抑制正常及不稳定膀胱逼尿肌自发性收缩频率及收缩强度 ,作用呈浓度依赖性 ,对DI组的作用强度明显低于正常对照组及梗阻后DS组 (P <0 .0 5 ) ;梗阻后DI组、对照组及梗阻组 β3 ARmRNA相对含量分别为 10 .2 7± 1.17、19.84± 2 .6 2和 18.38± 3.4 5 ,DI组明显降低 (P <0 .0 5 )。　结论　β3 AR激动剂能降低正常及梗阻后逼尿肌条自律性及收缩力 ,β3 AR密度变化可能参与大鼠BOO后逼尿肌不稳定的发生。     

同步膀胱膜部尿道测压的临床意义

目的 探讨同步膀胱膜部尿道压力测定的临床意义。方法 采用ANTEC Duet尿动力学仪同步测定412例泌尿系病人和6例健康者充盈和排尿时的膀胱和膜部尿道压力,肌电图用直肠电极测定。结果 （1）健康人充盈期膜部尿道压,男性为40－50cmH2O,女性为20－30cmH2O,充盈期膜部尿道压高于膀胱压,且全充盈期没有明显变化,排尿时膜部尿道压力明显下降低于膀胱压。（2）逼尿肌尿道协同失调的病人,排尿时膜部尿道压升高,其中逼尿肌外括约肌协同失调（EDES）时合并有肌电活动明显增加,逼尿肌膀胱颈协同失调（DBDS）肌电活动正常,排尿期尿道测压膀胱颈处压力呈斜坡样下降。（3）尿道关闭机制下降或不全时充盈期膜部尿道压明显低,且充盈期膜部尿道膀胱压力差为负值。（4）尿道不稳定充盈期膜部尿道压突然下降且幅度≥15cmH2O。（5）正常尿道腹压传递率为20％－35％,而压力性尿失禁（GUI）病人尿道腹压传递率＜20％。结论 同步膀胱膜部尿道压力测定操作简单,在判断尿道关闭机制的正常与否、逼尿肌尿道的协同与否、尿道稳定性及腹压向尿道的传递效率方面有重要价值。     

膀胱出口梗阻所致逼尿肌过度活动的神经电生理研究

目的 从膀胱传入神经以及盆底相关神经肌肉角度探讨神经因素及肌源性因素在膀胱出口梗阻所致的逼尿肌过度活动发生中的作用.方法 采用耻骨上膀胱颈梗阻的方法建立逼尿肌过度活动大鼠模型,测定不稳定收缩时盆神经传入电位信号,并同步测定阴部神经运动支电位、尿道外括约肌肌电及腹肌肌电的反射反应.并观察T8段脊髓截断、双侧盆神经截断、腹交感干截断以及双侧阴部神经截断后大鼠膀胱充盈测压不稳定收缩的变化.结果 成功制作了膀胱出口梗阻逼尿肌过度活动大鼠模型,成功率62.5%.充盈性膀胱测压神经肌电生理同步记录结果显示,允盈期逼尿肌过度活动可分为两种类型,一种为收缩幅度高于10 cmH2O(1 cmH2O=0.098 kPa)的逼尿肌过度活动(B-DO),伴有同步盆神经传入的信号明显增强,且能引发阴部神经、尿道外括约和腹肌肌电图出现显著变化;一种为收缩幅度低于10 cmH2O的逼尿肌过度活动(S-DO),没有上述盆神经传入及相关神经肌电变化.T8脊髓截断后,膀胱充盈-排尿收缩周期消失,膀胱基础压显著升高,B-DO消失,S-DO仍然存在,且收缩幅度较截断前略有上升,但差异无统计学意义.依次截断控制膀胱的盆神经、交感神经和阴部神经后,膀胱失去充盈-排尿收缩周期,基础压显著升高,不稳定收缩中B-DO消失,S-DO仍然存在.结论 膀胱出口梗阻所致的逼尿肌过度活动存在不依赖于中枢和周围神经的膀胱源性因素.     

逼尿肌自身肌源性变化与逼尿肌不稳定的关系

目的:探讨逼尿肌不稳定(Detrusor instability,DI)的发病机制。方法:建立Wistar大鼠膀胱流出道梗阻(Bladder outlet obstruction,BOO)动物模型,6周后行充盈性膀胱测压分出梗阻后稳定组和不稳定组,进行离体膀胱充盈性测压、逼尿肌条机械牵拉及胆碱类药物刺激试验。结果:不稳定组膀胱充盈至出现收缩时的压力明显低于稳定组及正常对照组,收缩发生时的容积明显低于稳定组;不稳定组逼尿肌条机械牵拉至其出现收缩时的最小张力明显低于稳定组及正常对照组;不同浓度氯化氨基甲酰胆碱刺激诱发的收缩频率各组间差异无统计学意义(P<0.05)。结论:逼尿肌不稳定的发生与逼尿肌自身的兴奋性增强密切相关。     

膀胱出口部分梗阻对逼尿肌生物力学特性的影响

目的 探讨膀胱出口部分梗阻(P-BOO)对膀胱逼尿肌生物力学特性的影响及机制.方法 采用Wistar雄性大鼠,膀胱颈不全结扎法建立P-BOO动物模型.依据梗阻时间分为假手术组、梗阻6周组(P-B006W)及梗阻12周组(P-B0012W),其中P-B006W组根据充盈性膀胱测压所示逼尿肌是否稳定分为逼尿肌稳定组(DS)和逼尿肌不稳定组(DI).采用灌流肌槽,以拟胆碱药物(氯化氨基甲酰胆碱)作为刺激因素,用拉力传感器测定离体逼尿肌条的主动收缩功能.充盈性膀胱测压检测最大膀胱容量、膀胱漏尿点压及膀胱顺应性的变化.结果P-BOO模型均成功建立,DI组最大膀胱容量、膀胱漏尿点压、膀胱顺应性[(10.8±3.0)ml,(39.4±7.1)cm H20,(0.27±0.08)ml/cm H20]、DS组[(10.3±1.9)ml,(35.9±6.2)cm H2O,(0.29±0.05)ml/cm H2O]及P-B0012W组[(9.5±2.3)ml,(48.6±9.5)cm H20,(0.21±0.05)ml/cm H2O]均明显高于假手术组[(2.1±0.3)ml,(16.2±2.1)cm H2O,(0.13±0.03)ml/cm H2O],差异有统计学意义(P＜0.05).DI组逼尿肌条拟胆碱药物刺激产生的收缩力显著低于假手术组和DS组.P-B0012W组逼尿肌条均未检测到明确的收缩波(波幅＜0.05 g).结论 P-BOO后膀胱逼尿肌生物力学特性发生了改变:DI组逼尿肌收缩功能受损,DS组发生代偿,但如果梗阻未解除,则逼尿肌收缩性损害,最终导致不可逆的收缩功能丧失;梗阻后膀胱顺应性增大与膀胱容积显著增加密切相关,逼尿肌稳定性对其影响不显著.     

电压依赖性钾通道和逼尿肌不稳定关系的实验研究

目的观察电压依赖性钾（Kv）通道在逼尿肌不稳定（DI）中的表达变化及作用，探讨DI的发生机理及Kv通道作为治疗靶点的可行性。方法25只雌性Wistar大鼠建立膀胱出口部分梗阻模型，6周后行膀胱测压获得DI模型。制备逼尿肌肌条，离体收缩实验观察Kv通道阻断剂对逼尿肌肌条自发性收缩功能的影响；RT-PCR技术检测逼尿肌中Kv通道mRNA的表达。10只正常大鼠为对照组。结果Kv通道阻断剂4-氨基吡啶干预后，对照组逼尿肌肌条的收缩频率、幅度变化率分别为（84．3±23．8）％、（45．9±16．1）％，DI组分别为（34．2±11．4）％、（14．2±5．1）％，DI组均低于对照组（P〈0．05）。对照组逼尿肌中Kv通道亚型Kv2．1、Kv1．5的相对含量分别为0．75±0．11、0．61±0．09，DI组分别为0．65±0．09、0．39±O．07，DI组Kv通道含量减少，其中Kv1．5减少更明显（P〈0．01）。结论Kv通道反馈调节逼尿肌收缩，此机制在DI组明显减弱，可能导致逼尿肌收缩过度活跃。DI组Kv通道作用下调可能与逼尿肌中Kv通道亚型特别是Kv1．5的mRNA表达减少有关。Kv1．5也许可以作为治疗DI的较好靶点。     

肾上腺素α1受体亚型与大鼠膀胱出口梗阻所致逼尿肌不稳定的关系

目的：探讨肾上腺素α1受体亚型与大鼠膀胱出口梗阻（BOO）所致逦尿肌不稳定（DI）的关系。方法：利用雄激素诱导前列腺肥大建立雄性SD大鼠膀胱出口梗阻模型,梗阻6周后行允盈性膀胱测压、离体逼尿肌条收缩实验及Western Blotting蛋白印迹实验。结果：BOO动物模型梗阻6周后逼尿肌不稳定的发生率为90％,DI组与对照组相比．排尿压力升高．（69．30±9．90）vs（49．60±8．36）cmH2O（P〈0．05）。剩残余尿量增加（0．29±0．07）vs（0,10±0．05）ml（P〈0．05）。膀胱容量增加（0．59±0．07）vs（0．23±0．05）ml（P〈0．05）。肌条收缩力升高（O．89±0．07）vs（0．43±0．05）g（P〈0．05）。α1D受体蛋白表达程度高于对照组,α1A受体表达程度未发生变化。结论：肾上腺素α1D受体主要参与到大鼠膀胱出口梗阻后逼尿肌不稳定的发生发展中。     

Effects of ligation of the internal iliac artery on blood flow to the bladder and detrusor function in rat

Ischaemia induced by atherosclerosis is a common cause of disorders in the elderly, including impairment of bladder function. To evaluate experimentally the effects of ischaemia on detrusor function, we performed infusion cystometry and evaluated the morphologic findings in the bladder of the rat. Blood flow to the bladder of the rat was evaluated with a Doppler flowmeter before and after the unilateral or bilateral ligation of the internal iliac arteries. Reevaluation was done at one and two weeks after surgery. Bladder function was studied by infusion cystometry performedin vivo under urethane anaesthesia. Finally, histological examination was performed. Blood flow at mid-dorsal wall of the control bladder was inversely related to intravesical volume. Unilateral or bilateral ligation of the internal iliac arteries decreased blood flow to the bladder, which showed a complete recovery two weeks postoperatively. Infusion cystometry of the ischaemic bladder with bilateral ligation of the internal iliac arteries demonstrated a decrease in voiding pressure, an increase in bladder capacity, and an increase in pressure at which micturition was initiated vs. the control. The bladder with unilateral ligation of the artery showed a decrease in voiding pressure, with no change in the other parameters. Histological examination indicated that the bilateral ischaemia and ischaemic side of unilateral ischaemia led to a degeneration of the mucosa, and severe oedema in submucosal and muscle layers one week postoperatively. Degeneration of smooth muscle was predominant at 2 weeks. Contralateral side of the unilaterally ischaemic bladder showed oedema and congestion of the submucosa and smooth muscle. Ligation of the internal iliac artery decreased blood flow to the bladder significantly, which resulted in smooth muscle degeneration. Consequently,in vivo voiding pressure was impaired in the ischaemic bladder.     

Suppression of detrusor overactivity in rats with bladder outlet obstruction by a type 4 phosphodiesterase inhibitor

OBJECTIVE: To investigate the effects of a selective type 4 cyclic nucleotide phosphodiesterase (PDE4) inhibitor, IC486051, on bladder activity in normal rats and those with and bladder outlet obstruction (BOO), as inhibition of PDE4 leads to elevation of intracellular cAMP levels and relaxation of smooth muscle. MATERIALS AND METHODS: BOO was induced in female Sprague-Dawley rats by tying a silk ligature around the urethra. At 4 or 6 weeks after inducing BOO, conscious rats were assessed by cystometry with the urethral ligature intact. In unobstructed rats, blood pressure was also measured. RESULTS: In unobstructed rats, IC486051 (0.1 mg/kg intravenously) produced no significant changes in cystometric variables, while at a dose of 0.5 mg/kg maximum voiding pressure was reduced by 34%. At both doses, there was a small, transient increase in blood pressure. In both 4- and 6-week BOO rats IC486051 dose-dependently decreased the number and amplitude of non-voiding bladder contractions by up to 80%, relative to pre-treatment values. At doses of 0.1 and 0.5 mg/kg IC486051 had no significant effect on voiding variables. In the 4-week BOO rats, a dose of 1.0 mg/kg decreased bladder capacity, voided volume and residual volume by 21%, 32% and 18%, respectively. In 6-week BOO rats, a dose of 1.0 mg/kg decreased maximal voiding pressure by 17% and pressure threshold for voiding by 28%. In both groups of rats with BOO, voiding efficiency was unchanged. CONCLUSIONS: A selective PDE4 inhibitor can effectively suppress detrusor overactivity in rats with BOO, at doses that have no effect on voiding bladder contractions. Thus, selective PDE4 inhibitors should be considered for the treatment of overactive bladder in patients with BOO.     

Effect of preemptive treatment of capsaicin or resiniferatoxin on the development of pre-micturition contractions after partial urethral obstruction in the rat

PURPOSE: Neuroplasticity in afferent pathways, including C-fiber bladder afferents, is believed to be one of the major causes of changes in bladder function after partial urethral obstruction. We determined if capsaicin sensitive C-fiber bladder afferents are involved in the development of pre-micturition contractions after partial urethral obstruction in the rat. MATERIALS AND METHODS: Female Wistar rats were preemptively treated with capsaicin (100 mg/kg subcutaneously) or resiniferatoxin (0.3 mg/kg subcutaneously) prior to the creation of obstruction. Before and 6 weeks after obstruction micturition profiles were compared among the 3 groups, including obstructed rats preemptively treated with capsaicin (BO/CAP) or resiniferatoxin (BO/RTX) and untreated obstructed rats (BO/-). In addition, conscious filling cystometry was performed after obstruction. RESULTS: Instillation of capsaicin solutions into the eye or bladder induced significant irritative reactions in BO/- but not in BO/CAP or BO/RTX, indicating that the effect of pretreatment with capsaicin or resiniferatoxin lasted 6 weeks. Voided volume per micturition on micturition profiles was decreased after partial urethral obstruction in all 3 groups. On conscious filling cystometry a significant increase in bladder capacity, voided volume and micturition threshold pressure was noted in BO/CAP but not in BO/RTX compared with BO/-. In contrast, there was no significant change in residual volume, voiding efficiency or micturition pressure among the 3 groups. The prevalence of pre-micturition contractions was 100% in BO/CAP and BO/RTX, and 83% in BO/-. CONCLUSIONS: Capsaicin sensitive C-fiber afferents are not essential to induce pre-micturition contractions but they are involved in functional alterations in bladder afferent pathways after partial urethral obstruction in rats.     

良性前列腺增生患者膀胱出口梗阻和逼尿肌功能的分析

目的：探讨尿动力学检查对BPH患者膀胱出口梗阻（BOO）和逼尿肌功能的诊断意义.方法：对95例BPH患者进行压力-容积和压力-流率测定.结果：95例BPH患者中BOO 57例,无BOO23例,其余15例为可疑或分析困难.BOO组前列腺体积大于无BOO组（62.4±16.1）cm^3 vs（41.0±7.1）cm^3（P＜0.05）,最大尿流率（Qmax）小于无BOO组（5.4±1.9）ml/s vs（12.4±5.0）ml/s（P＜0.05）,两组IPSS评分无差别（23.7±4.4）分vs（25.2±4.9）分（P＞0.05）.BOO组有逼尿肌不稳定收缩（DD34例,无BOO组D119例.结论：尿动力学检查有助于判断有无BOO存在,了解BPH患者的逼尿肌功能.IPSS不能判断患者的下尿路症状（LUTS）是否因BOO导致.BPH患者前列腺体积不足很大,但LUTS明显时,应行尿动力学检查.自由尿流率测定对BOO诊断有一定帮助.DI是无BOO患者发生LUTS的重要因素.     

Persistently increased voiding frequency despite relief of bladder outlet obstruction

PURPOSE: Bladder outlet obstruction (BOO) can increase urinary frequency. Even after surgical relief of obstruction, up to 30% of patient are still bothered by irritative voiding symptoms. We tested the hypothesis that deligation of a partial bladder outlet obstruction model mimics this clinical observation. MATERIALS AND METHODS: Female Wistar rats were obstructed for 3 weeks by partial urethral ligation and then were relieved of obstruction by urethral deligation. Measurements of voiding frequency and voided volumes were measured preoperatively, after ligation, and after deligation. Relief of obstruction was confirmed by measuring flow rates through ex vivo perfusion of deligated urethras. Urine osmolality and bladder weights were determined. Awake cystometrograms (CMGs) were performed 3 weeks after deligation to measure bladder function. RESULTS: Neither sham ligation nor sham deligation altered voiding frequency. Ligation doubled mean voiding frequency (in cc) from 2.01 +/- 0.32 to 3.96 +/- 0.22 per 4 hours (p = 0.0002). Three weeks after deligation, voiding behavior of the animals segregated into 2 groups: 20% had persistent hyperactive voiding frequency (6.67 +/- 1.23 per 4 hours) while 80% normalized voiding frequency (1.53 +/- 0.20 per 4 hours). The difference in voiding frequency in these 2 groups could not be attributed to alterations in urine osmolality, persistence of urethral obstruction, difference in bladder weights or severity of initial obstruction created. Awake CMGs revealed a higher peak micturition pressure and lower voided volume in the hyperactive voiders. CONCLUSIONS: 20% of the animals after urethral deligation had persistent hyperactive voiding which parallels clinical observations. Because the CMG data suggested persistent obstruction, yet urethral perfusion and bladder weights indicated no obstruction, we propose that these 20% of animals have a "functional" bladder outlet obstruction and can be used to study mechanisms underlying hyperactive voiding.