1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐对大鼠膀胱内压及前列腺增生的作用

在离体兔膀胱颈平滑肌 ,1 (2 ,6 二甲基苯氧基 ) 2 (3,4 二甲氧基苯乙氨基 )丙烷盐酸盐 (DDPH)使去氧肾上腺素所致平滑肌收缩的量效曲线平行右移 ,最大反应不变 ,pA2 值为 7.2 4 ;DDPH 2 5,50mg·kg- 1ig能显著降低麻醉大鼠膀胱容积 ,排尿压 ,排尿阈值压 ;DDPH 12 .5,2 5及 50mg·kg- 1·d- 1ig 4周还可抑制丙酸睾酮所致大鼠前列腺组织的增生 .实验结果提示DDPH有抗前列腺增生及改善尿流率的作用 .     

多沙唑嗪对映体对兔离体前列腺收缩反应的影响

目的观察多沙唑嗪[(±)Dox]及其对映体[(-)Dox和(+)Dox]对兔离体前列腺平滑肌收缩反应的影响。方法制备兔离体前列腺标本,记录药物诱发的前列腺肌条收缩反应。结果苯肾上腺素浓度依赖性诱发兔前列腺平滑肌收缩反应。(-)Dox、(+)Dox或(±)Dox拮抗苯肾上腺素诱发前列腺收缩反应的pKB值分别为8.14±0.17、8.12±0.14和8.11±0.21,三者之间差异无统计学意义(P>0.05)。(-)Dox、(+)Dox和(±)Dox均可显著性抑制电场刺激诱发的前列腺神经源性收缩反应(P<0.01),且三者的抑制作用强度差异无统计学意义(P>0.05)。结论多沙唑嗪对映体可抑制苯肾上腺素或电场刺激诱发的兔离体前列腺收缩反应,三者的抑制作用相同。     

萘哌地尔衍生物BWYJ抗前列腺增生的作用

目的观察萘哌地尔衍生物BWYJ对前列腺增生模型的作用。方法采用激素法建立去势大鼠和未去势小鼠前列腺增生模型,通过小鼠前列腺湿重,计算前列腺指数。光镜及透射电镜下,分别观察小鼠前列腺组织形态学及超微结构变化;TUNEL法检测BWYJ对大鼠前列腺细胞凋亡的影响。结果BWYJ5、10、20mg·kg-1组均可降低BPH小鼠前列腺湿重指数(P<0.05),光镜及电镜结果表明,BWYJ5、10、20mg·kg-1组均可抑制小鼠组织结构增生性变化,且BWYJ10、20mg·kg-1组使腺腔直径、腺体表面积变小(P<0.05)。TUNEL检测发现,大鼠前列腺凋亡细胞检出率较低,与模型组比较,BWYJ各剂量组差异无统计学意义(P>0.05)。结论BWYJ具有抗小鼠及大鼠良性前列腺增生作用。     

酚妥拉明、去氧肾上腺素对兔离体气管平滑肌收缩力的影响

目的 观察酚妥拉明及去氧肾上腺素对离体气管平滑肌张力的影响.方法 观察一定剂量的酚妥拉明、去氧肾上腺素对静息状态下离体兔气管平滑肌张力的影响;用电刺激诱发兔离体气管平滑肌收缩,观察一定剂量的酚妥拉明、去氧肾上腺素对其的影响.结果 酚妥拉明0.66mmol/L圾去氧肾上腺素1.23 mol/L对静息状态气管平滑肌无直接收缩作用(P＞.05).酚妥拉明0.66 mmol/L可显著抑制电刺激诱发的气管平滑肌收缩(P＜0.01).去氧肾上腺素1.23 mmol/L使电刺激兔离体气管平滑肌收缩力略有增加(P＞0.05).结论 酚妥拉明对电刺激诱发兔离体气管平滑肌收缩力有显著的抑制作用;去氧肾上腺素则无明显影响.     

盐酸小檗碱抑制大鼠良性前列腺增生诱发的下尿路症状

目的良性前列腺增生症(BPH)是一类在老年男性中常见的增生性泌尿系统疾病,其中大部分患者会发展表现为下尿路症状(LUTS)。寻找抑制膀胱平滑肌收缩的药物成为治疗BPH诱发的LUTS最有前景的策略之一。本文研究传统中药黄连(CCF)对BPH诱发的LUTS的抑制作用,并进一步探索其发挥作用的活性成分以及相关的分子机制。方法建立大鼠BPH模型,口服黄连提取物,用HE染色法检测前列腺和膀胱病理改变,计算前列腺指数PI和膀胱指数BI的变化。用肌条收缩舒张实验检测CCF及其活性成分盐酸小檗碱(Ber)对KCl或Ach诱导的膀胱逼尿肌的影响。用离体灌流法检测对排尿功能的影响。原代培养大鼠膀胱逼尿肌细胞,检测CCF和Ber对钙离子细胞内流和ROCK-1的表达的调控作用。结果 BPH大鼠前列腺和膀胱均表现出平滑肌明显增多的病理改变;其PI和BI值明显升高,并且出现排尿功能障碍;口服CCF可明显改善上述症状。CCF或Ber可以抑制Ach或KCL诱导的膀胱逼尿肌肌条收缩,并且显著延长大鼠排尿间隔,缩短大鼠排尿时间以及增加其排尿量。在机制方面,与CCF类似Ber可以抑制Ach诱导的钙离子细胞内流和ROCK-1的表达。结论 CCF以Ber为主要活性成分,具有调节膀胱平滑肌收缩的作用,可作为BPH-LUTS治疗的潜在药物。     

多沙唑嗪对映体对兔离体膀胱逼尿肌的作用及机制

目的观察多沙唑嗪(rac-DOX)及其对映体(S-DOX、R-DOX)对兔离体膀胱逼尿肌的作用并分析其机制。方法制备兔背侧和腹侧膀胱逼尿肌标本,记录药物或神经刺激诱发的膀胱平滑肌收缩反应。结果在兔背侧和腹侧膀胱逼尿肌标本,卡巴胆碱产生浓度依赖性收缩反应,两种标本的收缩反应差异无显著性(P>0·05)。在背侧膀胱逼尿肌标本,苯肾上腺素产生浓度依赖性收缩反应;但是,苯肾上腺素对腹侧膀胱逼尿肌无作用。S-DOX、R-DOX和rac-DOX在1μmol·L-1时,均可竞争性拮抗苯肾上腺素诱发的兔背侧膀胱逼尿肌收缩反应,其pKB值分别为7·44±0·19、7·39±0·14和7·38±0·30,三者的pKB值相同。电场刺激诱发兔背侧和腹侧膀胱逼尿肌产生稳定的收缩反应,该收缩反应被0·3μmol·L-1浓度的河豚毒素完全阻断。S-DOX、R-DOX和rac-DOX均抑制电场刺激诱发的背侧膀胱逼尿肌收缩反应(P<0·01),且三者的抑制作用强度差异无显著性(P>0·05);但是,它们对电场刺激诱发的腹侧膀胱逼尿肌收缩反应无影响。结论在兔离体膀胱背侧逼尿肌,S-DOX拮抗苯肾上腺素诱发收缩反应的pKB值与rac-DOX和R-DOX相同,三者尚能抑制电场刺激诱发的神经源性收缩反应。     

托特罗定合用坦索罗辛对实验性良性前列腺增生大鼠下尿路功能的影响

目的 观察托特罗定合用坦索罗辛对大鼠实验性良性前列腺增生致下尿路功能紊乱的改善作用.方法 健康雄性SD大鼠去势后,丙酸睾丸酮皮下注射制作前列腺增生模型.模型大鼠分别灌胃给予托特罗定(0.4 mg/kg),坦索罗辛(0.04 mg/kg)或托特罗定+坦索罗辛[(0.4+0.04)mg/kg]14 d,给药后测定前列腺指数,生理记录仪记录大鼠排尿波后采集排尿时间、排尿间隔时间、排尿点压、排尿压峰值等指标,并记录残余尿量和膀胱容积,观察药物对上述指标的改善作用.结果 托特罗定合用坦索罗辛可全面改善良性前列腺增生大鼠的排尿时间、排尿间隔时间、排尿点压和排尿压峰值,能够同时改善大鼠的尿频及排尿困难症状,并减少大鼠残余尿量(P＜0.05或P＜0.01).两药合用对膀胱容积无明显影响.结论 托特罗定合用坦索罗辛在有效减轻良性前列腺增生大鼠下尿路梗阻症状的同时,可有效降低其膀胱兴奋性,未增加良性前列腺增生大鼠的尿潴留危险,为临床治疗同时伴有梗阻和膀胱过度活动症状的前列腺增生患者提供了新的选择.     

复方遗尿冲剂对中枢的兴奋作用和对膀胱的抑制作用

用离体和在体方法研究复方遗尿冲剂对中枢神经系统的兴奋作用和对膀胱的抑制作用.结果显示,复方遗尿冲剂能缩短戊巴比妥钠催眠小鼠的睡眠时间,提高小白鼠的自主活动次数;能降低离体小鼠膀胱逼尿肌张力;明显延长麻醉兔的排尿时间间隔,降低膀胱最大充盈压,并有降低膀胱静息压力和增加膀胱最大容积的趋势,明显提高膀胱单位压力下最大容积的比值.结果提示,复方遗尿冲剂可能通过提高中枢神经系统兴奋性,增强皮层对脊髓排尿中枢的抑制作用以及抑制膀胱,提高排尿阈值而治疗遗尿.     

雌性大鼠产仔后膀胱功能的改变

目的比较产仔大鼠与未孕大鼠膀胱功能的差异。方法 6个月龄雌性大鼠34只,根据与雄鼠合笼后妊娠分娩与否分为2组:未孕大鼠组(16只)和产仔组大鼠(18只)。各组均做活体膀胱测压和离体膀胱肌条实验。结果产仔大鼠的排尿量、残余尿、膀胱顺应性和膀胱湿质量与未孕大鼠相似。与未孕大鼠相比,产仔大鼠最大膀胱容量、逼尿肌收缩的张力阈值和收缩频率增高,而其逼尿肌最大收缩力和逼尿肌平均收缩力降低。结论妊娠分娩可造成膀胱功能的损害,尤其是影响了膀胱的收缩功能。     

参桂提取物对实验性前列腺增生大鼠尿动力学的影响

目的 研究参桂提取物对大鼠实验性前列腺增生的治疗作用。方法将60只SD大鼠随机分为6组，每组10只。除假手术组外，其他5组大鼠均在无菌条件下行去势手术，术后1周分别皮下注射溶于橄榄油的丙酸睾丸酮，以制作前列腺增生模型。随后模型对照组给予0.9%氯化钠溶液，5 mL·kg 1；阳性对照组给予普乐安片，2.5 g·kg 1；参桂提取物低、中、高剂量组分别给予参桂提取物0.38 ，0.75和1.50 g·kg 1。假手术组给予假手术后，每天给予0.9%氯化钠溶液0.5 mL。所有大鼠均连续给药4周，末次给药后1 h称重，进行大鼠尿动力学测定，称取前列腺湿重和干重，计算湿重和干重指数。结果参桂提取物高、中剂量组大鼠每日以1.50和0.75 g·kg 1参桂提取物灌胃给药，连续4周后可抑制丙酸睾丸酮引起的大鼠前列腺增生，尿动力学参数明显改善，尿程延长，尿量增加，剩余尿量减少，排尿阈值压均有下降(P＜0.01或P＜0.05)；与模型组比较，前列腺湿重、湿重指数、干重及干重指数均下降（均P＜0.01）。结论参桂提取物可抑制大鼠前列腺增生，明显改善大鼠实验性前列腺增生导致的尿动力学参数。     

前列冲剂对前列腺增生大鼠血清酸性磷酸酶及T和E_2的影响

目的观察前列冲剂对前列腺增生大鼠血清前列腺特异性酸性磷酸酶活性和性激素水平的影响。方法50只SD雄性大鼠中,10只为正常对照组用蓖麻油造模。其余40只中,10只为模型组,另30只为实验组,给他们皮下注射丙酸睾丸酮(4ml/kg)诱导前列腺增生,实验组(分低、中、高剂量组)每天分别给予不同剂量前列冲剂(2.5ml/kg,5ml/kg,10ml/kg)灌胃。5周后将大鼠处死,摘取前列腺,称体重及前列腺湿重,计算前列腺指数;测定大鼠血清睾酮(T)、雌激素(E2)、总酸性磷酸酶(ACP)、非前列腺特异性酸性磷酸酶(NPAP),并计算前列腺特异性酸性磷酸酶(PAP)。结果中剂量和大剂量前列冲剂明显降低血清PAP,与模型组比较差异显著(P<0.01);明显拮抗实验性前列腺增生大鼠血清T水平升高(P<0.01),对血清E2水平无明显影响。中剂量(5ml/kg)和大剂量(10ml/kg)前列冲剂可以明显减少前列腺湿重和减小前列腺指数。结论前列冲剂有明显降低实验性前列腺增生模型大鼠血清PAP的作用,可以明显拮抗血清T水平的升高。前列冲剂抑制良性前列腺组织增生的作用与血清性激素水平变化有关。     

Effect of baicalein on experimental prostatic hyperplasia in rats and mice

We determined the effect of baicalein on prostatic hyperplasia in experimental animal models. Prostatic hyperplasia was induced by testosterone propionate in mice and castrated rats and by transplantation of homologous strain fetal mice urogenital sinus in mice. With the histopathological examination, the efficacy of baicalein on prostate hyperplasia in experimental animals was evaluated by the activity of serum acid phosphatase (ACP) and the following norm of the prostate gland: the volume, wet weight, wet weight index, dry weight index, DNA contents and prostatic epithelial height and cavity diameter. Results showed that baicalein at doses of 260 and 130 mg/kg administrated intragastrically (i.g.) significantly inhibited prostatic hyperplasia in castrated rats induced by testosterone propionate compared with the negative control group (p<0.01). Baicalein at doses of 520 and 260 mg/kg (i.g.) also significantly inhibited prostatic hyperplasia in mice induced by transplantation of homologous strain fetal mouse urogenital sinus and by testosterone propionate (p<0.01). These results suggested that baicalein has an inhibitory effect on prostatic hyperplasia in experimental animals.     

Preventive effects of D-004, a lipid extract from Cuban royal palm (Roystonea regia) fruits, on testosterone-induced prostate hyperplasia in intact and castrated rodents

Benign prostatic hyperplasia (BPH) is the noncancerous, uncontrolled growth of prostate gland cells and stroma that can cause difficulty urinating. Fruit lipid extracts from saw palmetto, a palm from the Arecaceae family, are used for BPH management. The Cuban royal palm, Roystonea regia, is also a member of the Arecaceae family and therefore it was appropriate to investigate the protective effects of Roystonea regia fruit lipid extracts on prostatic hyperplasia. The aim of this study was to investigate whether D-004, a lipid extract from Roystonea regia fruits, prevented testosterone-induced PH in castrated and intact rodents. Two series of experiments were performed. The first one was conducted in castrated and intact rats, distributed into five groups of 10 rats per group. The negative control group was injected with soy oil and treated orally with vehicle, while the four testosterone-injected groups were treated with vehicle (positive control), D-004 100, 200 and 400 mg/kg, respectively. The other experiment was conducted in castrated and intact mice. These were distributed into four groups of 10 mice per group: a negative control group and three testosterone-injected groups, of which one was a positive control, while two received D-004 200 and 400 mg/kg, respectively. At study completion, the rodents were sacrificed and prostates removed and weighed. D-004 at doses of 100, 200 and 400 mg/kg significantly and dose-dependently prevented prostate enlargement in intact and castrated rats and mice. The percentage inhibitions obtained in mice were greater: 77% and 84% for intact and castrated mice, respectively. D-004 therapy did not affect body weight. It is concluded that D-004 administered orally significantly prevented testosterone-induced prostate enlargement in both intact and castrated rodents, indicating that an endogenous supply of testosterone is not necessary to observe such an effect The results of the present investigation support further studies of D-004 on experimental models of prostatic hyperplasia.     

氟他胺与2-羟基氟他胺对大鼠前列腺增生的抑制作用(英文)

目的 :研究氟他胺与 2 羟基氟他胺对诱导的前列腺增生大鼠前列腺萎缩和细胞凋亡的作用。方法 :SD大鼠去势 ,皮下注射丙酸睾丸素诱导前列腺增生。前列腺增生大鼠随机分成以下 5组 :对照组、氟他胺组 5 0与 1 0 0mg·kg-1,2 羟基氟他胺组2 5与 5 0mg·kg-1,用药时间为 1 0d。比较前列腺各侧叶湿重 ,以HE染色及TUNEL染色法观察细胞凋亡并计算凋亡发生率。结果 :氟他胺及 2 羟基氟他胺可明显降低前列腺增生大鼠前列腺各侧叶湿重 ,差异有显著意义 ,并可观察到明显的凋亡细胞。结论 :氟他胺与 2 羟基氟他胺可诱导前列腺增生大鼠的前列腺萎缩和细胞凋亡     

Infravesical outflow obstruction in rats: a comparison of two models

1. A new model of infravesical outflow obstruction was developed in male rats by the repeated s.c. administration of testosterone for 5-15 days (3 mg/kg die). The effects of this treatment which produced a 65% increase of prostate weight (10 days) on bladder voiding was evaluated in urethane anesthetized rats by the transvesical infusion of saline and compared to the cystometric alterations produced by application of a silk ligature at urethral level in female rats (4-8 weeks before) as described by Malmgren et al. (1987a, b). 2. Testosterone-pretreatment for 10 days produced little changes in bladder weight, bladder capacity or amplitude of micturition contraction but determined a marked increase in residual volume, indicating that infravesical outflow obstruction impaired significantly bladder voiding. Furthermore, detrusor instability was observed in the majority of testosterone-treated rats. 3. The participation of an active component to voiding impairment in testosterone-treated rats was suggested by the effect of intravenous prazosin which improved voiding efficiency. 4. In urethra-ligated female rats there was a marked increase in bladder weight which was paralleled by a dramatic alteration in micturition reflex that is marked increase in bladder capacity and residual volume. 5. It is concluded that these two models of infravesical outflow obstruction produce cystometric patterns simulating the urodynamic alterations observed in patients with benign prostatic hyperplasia and are potentially suitable for development of drugs in this field.     

经尿道等离子前列腺切除前后尿动力学变化

目的观察经尿道等离子前列腺切除术(Transurethralplasmakineticpro-statectomy,TUPKP)治疗良性前列腺增生的效果。方法57例患者术前P/Q图检查及Schaefer分级和Lin-PURR定量分析确诊为良性前列腺增生伴膀胱出口梗阻(其中Ⅲ级11例,Ⅳ级18例,Ⅴ级21例,Ⅵ级7例),逼尿肌收缩强度弱加(W+)9例、正常减(N-)26例、正常加(N+)17例和强烈(ST)5例,分别进行术前、术后的国际前列腺症状评分和尿流动力学检查。结果与术前相比,IPSS评分由(25.47±4.67)分下降到(12.53±5.23)分,最大尿流率由(5.67±3.43)ml/s上升至(15.48±5.41)ml/s,而最大尿流率时膀胱逼尿肌压由(77.67±26.57)cmH2O下降至(37.12±29.46)cmH2O,膀胱容量由(235.84±157.17)ml升至(389.73±177.54)ml,前列腺长度明显减小,而压力变化不明显。结论经尿道前列腺等离子切除术可显著改善良性前列腺增生患者的膀胱流出道梗阻。     

Effect of terodiline hydrochloride on the function of urinary bladder in rats

The effect of terodiline on the function of urinary bladder was investigated in anesthetized rats. When saline was infused continuously into the urinary bladder of rats, terodiline (1-10 mg/kg, i.v.) prolonged the time to micturition in a dose-dependent manner. When enough saline was infused into the urinary bladder to induce the voiding contraction in urethra-ligated rats, terodiline (1-10 mg/kg, i.v.) and verapamil (1 mg/kg, i.v.) abolished the contraction, of which amplitude and frequency were partially inhibited by atropine (1 mg/kg, i.v.). Efferent discharge from the pelvic nerve on the micturition reflex was inhibited by terodiline (3 mg/kg, iv.v.). Both of the bladder contractions evoked by the electrical stimulation of the peripheral or central cut end of the pelvic nerve were dose-dependently inhibited by terodiline (1-10 mg/kg, i.v.). At 3 mg/kg or more, terodiline significantly inhibited the contraction, and the effects were long lasting. The effect of atropine (1 mg/kg, i.v.) was similar to that of terodiline (3 mg/kg, i.v.). Increase in frequency of urination and decrease in total urinary volume per micturition after the bilateral transection of the hypogastric nerve were improved after on oral administration of terodiline (1-10 mg/kg).