摘要
目的 探讨5型磷酸二酯酶抑制剂对不稳定膀胱的作用及可能途径.方法 成年自发性高血压模型SD雄性大鼠24只,随机数字表法分为每日灌胃组、间断灌胃组和空白组,每组8只,每日灌胃组：每日伐地那非（10mg·kg-1·d-1）灌胃;间断灌胃组：每隔3 d伐地那非（10 mg·kg-1·d-1）灌胃;空白组：每日生理盐水灌胃.另以8只成年雄性SD大鼠为对照组,行每日生理盐水灌胃.2周后4组分别行膀胱尿动力学检查.各取4组大鼠膀胱逼尿肌分为2份,用于观察预收缩后硝普钠、Rho激酶抑制剂Y-27632对大鼠膀胱逼尿肌舒张作用的影响及用酶联免疫法测定组织中环磷酸鸟苷（cGMP）含量.结果 空白组膀胱排尿间隔时间及膀胱容量均小于对照组[（409±36）s比（568±60）s;（284±25） μl 比 （395±42）μl,均P〈0.01]、储尿期膀胱收缩次数大于对照组[（2.03±0.49） 次/min比（1.07±0.30）次/min,P〈0.01];间断及每日灌胃组上述指标[（486±53）s 和 （564±44）s;（337±37）μl 和（392±30） μl;（1.82±0.32 ）次/min和 （0.52±0.23） 次/min]较空白组明显改善（P〈0.05）;且每日灌胃组作用更为显著（P〈0.01）.间断及每日灌胃组与空白组比较,膀胱逼尿肌对硝普钠敏感性较强[最大舒张率：（50.6±2.1）% 和（67.9±4.1）%比（25.3±5.0）%,P〈0.01],对Y-27632的敏感性较弱[（35.8±2.5）% 和（20.2±2.3）%比（71.6±2.8）%,P〈0.01],组织cGMP含量较高[（20.6±4.1） fmol/mg和（29.4±4.3） fmol/mg比（12.9±2.1） fmol/mg,P〈0.01];且每日灌胃组更为明显（P〈0.01）.结论 高血压模型大鼠膀胱逼尿肌存在不稳定收缩,5型磷酸二酯酶抑制剂能有效治疗不稳定膀胱,且持续每日干预效果更佳.5型磷酸二酯酶抑制剂改善膀胱逼尿肌不稳定收缩可能与cGMP介导的蛋白激酶G-RhoA/Rho激酶途径有关.
Objective To investigate the effects and the possible mechanistic pathway of phosphodiesterase type 5 （PDE5） inhibitors on rats with overactive bladder. Methods A total of 24 adult male spontaneously hypertensive rats （SHRs） were randomly divided into 3 groups： daily lavage group, discontinuous lavage group and blank group （n=8 each）. Daily vardenafil （10 mg·kg-1·d-1）, discontinuous vardenafil （10 mg·kg-1·d-1） and daily normal saline were administered respectively to 3 groups by lavage. And 8 adult male SD rats were included into the control group. Bladder urodynamic examinations were conducted in each group 2 weeks later. Then bladder detrusor muscle strips isolated from each group were further divided into two parts. One part was first pre-contracted and then the relaxant effects of sodium nitroprusside and Y-27632 were observed. For another part, enzyme-linked immunosorbent assay was used to measure cyclic guanosine monophosphate （cGMP）. Results As compared with the control group, the values of bladder intercontraction interval （ICI） and bladder capacity （BC） were significantly lower [（409±36）s vs （568±60）s,（284±25） μl vs （395±42）μl,P〈0.01] while the bladder nonvoiding contraction （NVC） was significantly higher in the blank group[（2.03±0.49） number/min vs（1.07±0.30）number /min,P〈0.01]. Compared with the blank group, the values of ICI and BC were elevated. NVC decreased obviously in the discontinues and daily lavage groups [（486±53）s and （564±44） s;（337±37）μl and （392±30） μl;（1.82±0.32 ）number/min and （0.52±0.23） number/min,P〈0.05]. The effects were more significant in the daily lavage group （P〈0.01）. The maximal relaxant effect of sodium nitroprusside was obviously enhanced in the discontinues and daily lavage groups [（50.6±2.1）% and （67.9±4.1）% vs（25.3±5.0）%,P〈0.01]. However the sensitivity of Y-27632 decreased significantly [（35.8±2.5）% and （20.2±2.3）% vs （71.6±2.8）%,P〈0.01], while the level of cGMP was significantly higher in the bladder detrusor muscle [（20.6±4.1） fmol/mg and （29.4±4.3） fmol/mg vs （12.9±2.1） fmol/mg,P〈0.01]. The effects of the daily lavage group were more pronounced （P〈0.01）. Conclusion The phenomenon of bladder overactivity is observed in the SHRs. The PDE5 inhibitors are effective in treating overactive bladder. And the effect of daily supplement is much better. In addition, the mechanism may operate through the cGMP-dependent protein kinase G-RhoA/Rho kinase signaling pathway.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2011年第28期2001-2005,共5页
National Medical Journal of China
