α1D与α1A受体亚型对大鼠不稳定逼尿肌收缩功能的影响

目的研究α1D及α1A受体亚型对大鼠膀胱出口梗阻（BOO）引起的不稳定逼尿肌（D1）收缩性、自律性的影响。方法建立Wistar大鼠BOO模型，充盈性膀胱测压确定D1模型，通过离体肌条牵拉实验，记录高选择性α1D及α1A受体亚型拮抗剂作用下，D1组和假手术对照组肌条自发性收缩频率及收缩力变化。结果35只BOO模型大鼠存活32只，D1发生率为71．9％。在一定张力前负荷下离体逼尿肌均产生自发性收缩，D1组肌条自发性收缩频率及收缩力均明显高于对照组；α1受体激动剂苯福林（PE）可使肌条自发性收缩频率及收缩力增加，选择性α1A受体拮抗剂5-MU能降低[（2．43±0．71）次／min，（0．14±0．03）g]对照组肌条的自发性收缩频率（2．64±0．72）次／min及收缩力（O．20±0．04）g，也能拮抗[（2．37±0．57）次／min，（0．19±0．02）g]PE所致的对照组肌条收缩频率（4．22±0．37）次／min和收缩力（0．31±0．03）g的增加（P〈O．01），而对D1逼尿肌作用不明显。选择性α1D受体拮抗剂BMY7378能降低[（2．32±0．56）次／min，（0．18±0．04）g]DI组肌条的自发性收缩频率（5．06±1．02）次／min及收缩力（0．42±0．08）g，并拮抗[（4．28±0．71）次／min，（0.48±0．04）g]PE所致的肌条收缩频率（6．73±0．61）次／min和收缩力（0.95±0．07）g的增加，但对正常逼尿肌作用不明显。结论 α1受体兴奋可使逼尿肌收缩频率及收缩力增加，正常逼尿肌中α1受体主要通过α1A亚型发挥作用，而梗阻性不稳定逼尿肌则主要通过α1D亚型发挥作用。     

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。     

前列冲剂对雄性大鼠离体膀胱逼尿肌作用的研究

目的观察前列冲剂对雄性大鼠离体膀胱逼尿肌运动的影响，并初步探讨其作用机制。方法运用BL-420型生物信号系统记录离体大鼠膀胱逼尿肌肌条的活动，观察不同剂量前列冲剂对大鼠膀胱逼尿肌自发活动的影响，并分析其作用机制。结果前列冲剂对大鼠膀胱逼尿肌有明显的兴奋作用，可增加其收缩时间、最大收缩张力及膀胱活动力，并呈量效关系。该作用可被异搏定（L型电压依从性Ca2＋通道阻断剂）和阿托品部分阻断（P〈0.01）。结论前列冲剂在体外可增强膀胱平滑肌的收缩，其作用是通过多条途径发挥的，尤其是通过L型钙通道和胆碱能M型受体而起作用的。     

胆固醇对胆固醇结石形成和胆囊离体肌条的影响

目的 探讨胆固醇与胆囊动力的关系及其在胆固醇结石形成中的作用.方法 构造豚鼠胆固醇结石模型,检测各组豚鼠血清胆固醇(TC)及胆汁胆固醇(BC)含量;利用灌流法加药,张力换能器记录胆囊收缩素对各组离体胆囊肌条张力的变化,并初步探讨胆固醇对胆囊肌条的作用机制.结果 A组(正常豚鼠)无结石发生,B、C两组(致石饲料4周、8周)共有13例结石发生;B、C两组TC和BC升高(与A组相比P<0.05),加入CCK后收缩振幅均增加,呈浓度依赖性.且与TC、BC相关(P<0.05);同A组相比,B、C及D(胆固醇孵育后胆囊肌条)三组对CCK效应值变小,起作用时间慢(P<0.05);CCK对胆囊离体肌条的作用可以部分被胆固醇抑制(变化为69.2%,P<0.05),而胆固醇的影响可以部分被阿托品、尼莫地平抑制(变化分别为64.2%、62.1%,P<0.05),不被TTX影响(P>0.05).结论 TC及BC增高的同时胆囊肌条肌张力降低及对CCK的敏感性降低,成石率增高;胆固醇孵育后肌条肌张力降低及对CCK的敏感性降低;胆固醇可能与胆囊动力及胆固醇结石形成相关.     

胆固醇对胆固醇结石形成和胆囊离体肌条的影响

目的 探讨胆固醇与胆囊动力的关系及其在胆固醇结石形成中的作用.方法 构造豚鼠胆固醇结石模型,检测各组豚鼠血清胆固醇(TC)及胆汁胆固醇(BC)含量;利用灌流法加药,张力换能器记录胆囊收缩素对各组离体胆囊肌条张力的变化,并初步探讨胆固醇对胆囊肌条的作用机制.结果 A组(正常豚鼠)无结石发生,B、C两组(致石饲料4周、8周)共有13例结石发生;B、C两组TC和BC升高(与A组相比P<0.05),加入CCK后收缩振幅均增加,呈浓度依赖性.且与TC、BC相关(P<0.05);同A组相比,B、C及D(胆固醇孵育后胆囊肌条)三组对CCK效应值变小,起作用时间慢(P<0.05);CCK对胆囊离体肌条的作用可以部分被胆固醇抑制(变化为69.2%,P<0.05),而胆固醇的影响可以部分被阿托品、尼莫地平抑制(变化分别为64.2%、62.1%,P<0.05),不被TTX影响(P>0.05).结论 TC及BC增高的同时胆囊肌条肌张力降低及对CCK的敏感性降低,成石率增高;胆固醇孵育后肌条肌张力降低及对CCK的敏感性降低;胆固醇可能与胆囊动力及胆固醇结石形成相关.     

钙激活通道对不稳定逼尿肌条收缩功能调节的实验研究

目的探讨钙激活钾通道和氯通道对逼尿肌条收缩的调节在逼尿肌不稳定发生中的作用.方法建立Wistar大鼠逼尿肌不稳定模型,设正常对照组,利用逼尿肌条体外实验,观察阻断与开放通道后肌条的收缩频率和动力指数变化及差异.结果对照组与不稳定组肌条收缩频率分别为(2.3±0.5)次/min和(4.1±0.9)次/min,动力指数分别为31.3±6.1和59.5±7.8,2组比较差异有统计学意义(P＜0.01).2组逼尿肌条的收缩频率和动力指数在钙激活钾通道阻断与开放前后的增加或下降变化均有统计学意义(P＜0.05),其中对照组大电导钙激活钾通道阻断后频率下降(23±10)%,不稳定组增加(29±10)%,2组动力指数分别增加(24±5)%和(16±5)%,通道开放后频率分别下降(34±7)%和(23±9)%,动力指数分别下降(32±9)%和(23±7)%.2组小电导钙激活钾通道阻断后频率分别增加(77±16)%和(27±10)%,动力指数分别增加(81±12)%和(52±14)%,通道开放后频率分别下降(49±6)%和(35±7)%,动力指数分别下降(55±8)%和(32±12)%.2组钾通道阻断或开放前后变化幅度的差异有统计学意义(P＜0.01).对照组阻断钙激活氯通道后收缩频率及动力指数下降(9±20)%和(8±9)%(P＞0.05),不稳定组分别下降(44±17)%和(50±12)%(P＜0.01),2组变化幅度差异有统计学意义(P＜0.01).结论钙激活钾通道和氯通道反馈调节逼尿肌收缩功能,钾通道作用下降和氯通道作用增强可能是导致梗阻性逼尿肌不稳定的重要原因之一.     

西地那非对豚鼠离体膀胱收缩的抑制作用

膀胱过度活动症是过度活动的逼尿肌不随意的或无限制的收缩,在医学上,大多数病例常常使用抗胆碱能药物治疗。近来,已有其他可选药物用于治疗逼尿肌不稳定。一些实验和临床研究表明,磷酸二脂酶在平滑肌张力的调控中起到很大作用,在本次研究中,Onur R等评估了西地那非(万艾可)对离体豚鼠膀胱在激动剂作用下收缩的影响[Turk UrolojiDergisi,2005,31:(1)12-16]。共宰杀了10只体重400-450 g的成年豚鼠,经腹部中线切口,暴露膀胱后,完整将膀胱从周围组织分离,所有膀胱都被放置在盐水溶液中,然后制备膀胱条带,大小为10 mm×2 mm的离体豚鼠膀胱条带…     

心痛定、阿托品对豚鼠离体胆囊平滑肌条收缩的研究

为进一步阐明心痛定治疗胆绞痛、引起胆汁淤积，诱发胆结石形成的机制，作者用心痛定与阿托品在豚鼠离体胆囊平滑肌条上进行对比研究。     

丹参对急性胰腺炎三磷酸肌醇及钙代谢的影响

目的 观察丹参对重症急性胰腺炎(SAP)时三磷酸肌醇(IP3)及钙代谢的影响.方法 30只SD大鼠随机等分为3组:SAP模型组(SAP组)、丹参治疗组(T组)和对照组(C组).SAP组和T组以3%牛磺胆酸钠诱发SAP模型,后者术后注射丹参.观察18 h各组胰腺细胞IP3和细胞内钙(Ca~(2+))、血清肿瘤坏死因子(TNF)-α、血清钙(血钙)和淀粉酶(AMY),以及胰腺的病理改变(PSP).结果 SAP组IP3、Ca~(2+)、TNF-α、AMY和PSP显著高于T组和C组(P<0.05),C组明显低于T组(P<0.05),且IP3与Ca~(2+)和TNF-α及后两者间呈明显正相关(P<0.05);血钙则是SAP组显著低于T组和C组(P<0.05),C组明显高于T组(P<0.05),IP3、Ca~(2+)和TNF-α与血钙为明显负相关(P<0.05).结论 丹参可抑制大鼠SAP时IP3释放,调节钙代谢,使胰腺病理损害减轻.     

双氯灭痛对膀胱逼尿肌收缩的影响及临床应用

双氯灭痛对膀胱逼尿肌收缩的影响及临床应用徐耀庭，陈修诚，李文广，常威我们观察了双氯灭痛对豚鼠膀胱逼尿肌收缩的影响以及治疗下尿路术后并发的膀胱无抑制性收缩患者的疗效，现报告如下。材料与方法试验组用健康成年豚鼠１２只，体重４００～５００ｇ。处死后，于膀胱...     

The treatment of detrusor instability

Detrusor instability is a common cause of urinary symptoms, including incontinence. It severely affects the quality of life of thousands of women and at present many of the available treatments lack efficacy, specificity, or are associated with unacceptable side effects. The treatment methods currently in use will be reviewed.     

The effect of urethral pressure variation on detrusor activity in women

The purposes of this study were to confirm previously described patterns of urethral pressure variation and to establish criteria for their diagnosis. The effect of urethral pressure variation on detrusor activity was also examined. The study involved a retrospective review of the computerized cystometric tracings from a 26-month period. Forty-one patients had artefact-free satisfactory tracings demonstrating urethral pressure variation, detrusor instability and/or gradual detrusor pressure increase. These tracings were stored on a computer program which permitted real-time second-by-second review. Statistical analysis was done using Fisher's exact test and an independentt-test. Three patterns of urethral pressure variation were identified: rapid pressure variation (RPV), gradual pressure variation (GPV) and stress-induced transient urethral relaxation (SITUR). RPV was associated with onset at low bladder volumes (independentt-test,P=0.02) and with detrusor instability (Fisher's exact test,P<0.001). GPV began at high bladder volumes (Fisher's exact test,P<0.001). SITUR was not associated with any specific pattern of urethral pressure variation or detrusor pressure change. Analysis of tracings of the patients with a combination of rapid urethral pressure variation and detrusor instability revealed a statistically significant increased frequency of urethral relaxation as the primary event precipitating an unstable detrusor contraction (Fisher's exact test,P<0.003). In conclusion, three different patterns of urethral pressure variation were identified. Rapid pattern urethral pressure variation is closely associated with detrusor instability. Further study of urethral pressure variation may help to elucidate the pathophysiologic mechanism responsible for idiopathic unstable detrusor contractions.Editorial Comment: This investigation includes very interesting and clinically important findings. The authors describe three patterns of urethral pressure variation and their relation to the detrusor activity. Taking these activities of the urethra into consideration, especially the relationship between detrusor instability and rapid urethral pressure variation, we may select the reasonable and effective therapeutic modality for female urinary incontinence. This study is timely, adding pertinent information for clinical decision-making.     

The clam enterocystoplasty in the treatment of idiopathic detrusor instability

Enterocystoplasty is being used increasingly frequently in the treatment of both idiopathic detrusor instability and neuropathic bladder dysfunction. After operation, most patients with idiopathic detrusor instability and disabling urinary incontinence refractory to previous treatments, experience improvements in continence and urgency, but residual symptoms are common. Detrusor instability can be demonstrated in over half of patients after operation, but significant decreases in the severity of instability are found after operation as assessed by the volume at first unstable contraction.Enterocystoplasty is a major operation with the potential for postoperative morbidity and mortality. In addition, the improvements in symptoms are bought at a price: increases in residual urine are common, and in the long term many patients need to perform clean intermittent self-catheterization, and some experience recurrent urinary infections. Patients about to undergo enterocystoplasty should be carefully selected and should be trained in the use of CISC. In selected patients with severe refractory idiopathic detrusor instability, the procedure can yield satisfactory results.     

前列腺增生症病人的逼尿肌收缩力减弱与剩余尿

应用压力流率测定技术，经Ｓｃｈ¨ａｆｅｒ列线图和直线被动尿道阻力关系（ＬｉｎＰＵＲＲ）定量分析９５例前列腺增生症病人的逼尿肌收缩强度。逼尿肌收缩强度分为四级：很弱（ＶＷ）、弱（Ｗ）、正常（Ｎ）和强（ＳＴ）。导管法结合压力流率测定时膀胱灌注量与排出量之差确定剩余尿。结果表明，逼尿肌收缩力很弱和弱与收缩力正常和强的病人之间存在显著性差异（Ｐ＜０．００１）。剩余尿量随逼尿肌收缩力减弱而增加。逼尿肌收缩力很弱的病人术后剩余尿量未改善；逼尿肌收缩力弱的病人术后逼尿肌收缩力可能改善，剩余尿减少；逼尿肌收缩力正常或强的病人术后剩余尿明显减少。     

逼尿肌不稳定缝隙连接介导细胞间通讯的研究

目的　研究逼尿肌不稳定 (DI)缝隙连接介导的细胞间通讯 (GJIC)功能 ,探讨DI发病机理以及阻断兴奋传递作为治疗手段的可行性。　方法　采用荧光光漂白恢复技术 (FRAP)检测BOO大鼠模型培养膀胱逼尿肌细胞GJIC功能 ,以荧光恢复率作为比较。　结果　在漂白后第 4min时 ,DI组平均荧光恢复率为 (35 .791± 0 .836 ) % ,正常对照组为 (8.6 4 5± 0 .6 73) % ,DI组显著高于对照组 (P <0 .0 1) ,差异有显著性意义。　结论　细胞间兴奋传递增强是DI发生的重要原因之一。     

投射逼尿肌等容收缩压1在评价女性逼尿肌收缩力中的应用

目的 探讨投射逼尿肌等容收缩压1(PIP1)在评价女性逼尿肌收缩力中的应用.方法 女性患者112例,平均年龄55(18～84)岁.其中腰椎间盘突出症58例.均行尿动力学检查,PIP1以公式P_(det) Q_(max)+Q_(max),计算.统计学分析PIP1与患者年龄、WF_(max)、膀胱初始感觉、膀胱最大容量的相关性.112例患者分为PIP1降低组(＜30 cm H_2O,1 cm H_2O=0.098 kPa)、正常组(30～75cm H_2O)和升高组(＞75 cm H_2O),58例腰椎间盘突出症患者分为术前、术后组,比较各组间的尿动力学参数.结果 112例患者平均PIP1为(42.6±16.3)cm H_2O,平均P_(det) Q_(max)(29.2±15.2)cm H_2O,平均Q_(max)(13.3±7.3)ml/s,平均WF_(max)(9.2±5.4)μW/mm~2.PIP1与年龄(r=0.343,P=0.000)、WF_(max)(r=0.540,P=0.000)之间有显著相关性.PIP1降低组、正常组、升高组之间年龄(P=0.006)、P_(det) Q_(max)(P=0.000)、Q_(max)(P=0.003)、WF_(max)(P=0.000)差异有统计学意义.58例腰椎间盘突出症患者术前、术后平均PIP1分别为(44.4±14.2)、(35.4±13.5)cm H_2O,平均P_(det) Q_(max)分别为(29.3±13.2)、(23.6±11.2)cm H_2O,平均Q_(max)分别为(15.1±7.7)、(11.8±5.9)ml/s,患者术后PIP1显著下降(P=0.027),组间P_(det) Q_(max)(P=0.114)和Q_(max)(P=0.122)差异无统计学意义.结论 PIP1适于评价女性逼尿肌收缩力,PIP1与年龄和WF_(max)有显著相关性.     

The effect of intravesical ketoprofen on acetylcholine-evoked urinary bladder contractility and detrusor overactivity in the anesthetized rabbit model

Intraurethral procedures such as the transurethral resection of the prostate can generate detrusor overactivity and bladder irritability. The rabbit model of detrusor overactivity has proven to be an excellent model to study the effects of drugs on detrusor overactivity. Using this model, we evaluated the responses to intravesical ketoprofen. In this model, each rabbit is anesthetized and the right external carotid artery is cannulated for blood pressure monitoring. A catheter is inserted through the femoral artery and is used for administration of acetylcholine (Ach). The bladder is exposed and catheterized for bladder pressure monitoring and drug addition and the proximal urethra is ligated. Cystometry is performed, the bladder drained, and 20 ml buffer placed in the bladder. After 30 min Ach is injected proximal to the vesical artery and the response of the bladder and blood pressure is recorded. Ach administration is repeated at 10-min intervals until three consistent responses are obtained. The bladder is drained and 20 ml of ketoprofen (100 μM final concentration) is placed in the bladder. Ach injections are repeated as given above at 10 min intervals and observed for 4 h. At the end of the experiment, a second cystometry is performed. The following is a summary of the results: Ketoprofen had no effect on either micturition pressure or the intravesical volume at micturition. Ketoprofen administration resulted in a progressive 50% decrease in the response to Ach. Ketoprofen mediated a progressive decrease in detrusor overactivity amplitude and frequency, reaching a maximum at 120–180 min. This material is based upon work supported in part by from grants from Omerous; in part by the Office of Research and Development, Department of Veterans Affairs, and in part by NIH grant RO-1-DK 067114.     

A rat model for investigation of spinal mechanisms in detrusor instability associated with infravesical outflow obstruction

Summary A rat model of infravesical outflow obstruction was modified to allow cystometric investigation in conscious, free-moving animals after intrathecal drug administration. The catheter position and extent of drug distribution were controlled by injection of dye and dissection of the spinal canal. Continuous cystometries were performed in awake normal rats as well as rats with bladder hypertrophy and hyperactivity following infravesical outflow obstruction. In some animals of each group, cystometry was performed with simultaneous recording of intra-abdominal pressure. The possible effects of the presence of the intrathecal catheter were studied, as well as the effects of saline, local anesthetics, morphine and naloxone administered through the catheter. Neither the presence of the intrathecal catheter nor injection of saline affected the cystometric pattern. Bupivacaine (50 g) produced paralysis of both lower extremities and a complete, though reversible, suppression of micturition in normal rats. In rats with hypertrophy, intrathecal bupivacaine in doses of 50 g and 100 g produced decreases in micturition pressure, increases in bladder capacity and dribbling incontinence. However, the amplitude of spontaneous contractile activity increased after the administration. The inhibitory effects of morphine (0.5–10 g) on micturition in normal rats, which were rapidly reversed by naloxone, were in accordance with results obtained in previous studies in anesthetized animals. Rats with bladder hypertrophy showed a similar response to morphine and naloxone. However, the bladder hyperactivity was not inhibited by morphine. We conclude that the present model seems reliable for the study of spinal mechanisms in the development of detrusor instability associated with infravesical outflow obstruction.     

前列腺增生症患者剩余尿与膀胱出口梗阻逼尿肌收缩力的相关性研究

目的 :探讨前列腺增生症 (BPH)患者剩余尿 (RUV )与膀胱出口梗阻 (BOO)、逼尿肌收缩力相关性。方法 :对 42例 BPH患者进行尿动力学检查。结果 :RUV与 BOO呈正相关 (r =0 .716 0 ,P <0 .0 1) ,与逼尿肌等容收缩压 (Piso)呈负相关 (r =- 0 .5 718,P <0 .0 1)。术前和术后的 RU V、尿道阻力因子 (URA )的差异有显著性意义 (P<0 .0 5 ) ,而术前和术后的 Piso差异无显著性意义 (P>0 .0 5 )。结论 :BPH患者 RUV的产生及增多是由于 BOO的加重和逼尿肌功能受损的共同结果 ,在病程的不同阶段 ,BOO和逼尿肌收缩力对 RUV的产生、增多及减少具有不同的作用和意义。     

The influence of changes in extracellular and intracellular sodium concentration on detrusor contractility

OBJECTIVE: To determine the role of Na+-Ca2+ exchange in the regulation of isolated detrusor smooth muscle contractility. MATERIALS AND METHODS: Isolated guinea-pig detrusor strips were used to record isometric tension generated by; (a) electrical-field stimulation to elicit nerve-mediated responses; and (b) adding carbachol or superfusing with a high-K+ solution. The [Na+] gradient between extracellular and intracellular compartments was altered by: (i) reducing superfusate [Na+] in stages from 140.2 to 10.2 mm; (ii) addition of the cardiac glycoside strophanthidin (200 microm). RESULTS Reducing extracellular [Na+] reversibly reduced the magnitude of nerve-mediated contractions but increased the resting tension and magnitude of carbachol-induced contracture. The mean (sd) [Na+] required for a half-maximum effect on attenuating contractions, at 85.9 (6.2) mm, and developing contracture, at 59.1 (14.3) mm, were significantly different. The time constants of changes to nerve-mediated contractions and carbachol contracture were also significantly different, at 147 (5) vs 1207 (386) s, respectively. These differences suggest that separate mechanisms influence nerve-mediated contraction and contracture in low-Na+ solutions. Exposure to the cardiac glycoside strophanthidin produced a similar effect to low-Na+ solutions for carbachol contracture. Low-Na+ solutions had no significant effect on contractures induced by high extracellular [K+]. CONCLUSION Reducing the transmembrane [Na+] difference increases intracellular [Ca2+]. This increase is largely accommodated in intracellular stores, that can be released by exogenous carbachol. The results are consistent with the presence of a functional Na+-Ca2+ exchanger in the surface membrane. The lack of effect of low-Na+ solutions on contractures evoked by membrane depolarization is consistent with this conclusion. The reduction of the nerve-mediated contraction by low-Na+ solution might result from blockade of the nerve action potential.