中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2011年
28期
2001-2005
,共5页
陈洪德%叶雪挺%翁志梁%李澄棣
陳洪德%葉雪挺%翁誌樑%李澄棣
진홍덕%협설정%옹지량%리징체
大鼠,近交SHR%磷酸二酯水解酶类%Rho激酶%膀胱逼尿肌
大鼠,近交SHR%燐痠二酯水解酶類%Rho激酶%膀胱逼尿肌
대서,근교SHR%린산이지수해매류%Rho격매%방광핍뇨기
Rats,inbred SHR%Phosphoric diester hydrolases%Rho kinase%Bladder detrusor muscle
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.
目的 探討5型燐痠二酯酶抑製劑對不穩定膀胱的作用及可能途徑.方法 成年自髮性高血壓模型SD雄性大鼠24隻,隨機數字錶法分為每日灌胃組、間斷灌胃組和空白組,每組8隻,每日灌胃組：每日伐地那非(10mg·kg-1·d-1)灌胃;間斷灌胃組：每隔3 d伐地那非(10 mg·kg-1·d-1)灌胃;空白組：每日生理鹽水灌胃.另以8隻成年雄性SD大鼠為對照組,行每日生理鹽水灌胃.2週後4組分彆行膀胱尿動力學檢查.各取4組大鼠膀胱逼尿肌分為2份,用于觀察預收縮後硝普鈉、Rho激酶抑製劑Y-27632對大鼠膀胱逼尿肌舒張作用的影響及用酶聯免疫法測定組織中環燐痠鳥苷(cGMP)含量.結果 空白組膀胱排尿間隔時間及膀胱容量均小于對照組[(409±36)s比(568±60)s;(284±25) μl 比 (395±42)μl,均P<0.01]、儲尿期膀胱收縮次數大于對照組[(2.03±0.49) 次/min比(1.07±0.30)次/min,P<0.01];間斷及每日灌胃組上述指標[(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]較空白組明顯改善(P<0.05);且每日灌胃組作用更為顯著(P<0.01).間斷及每日灌胃組與空白組比較,膀胱逼尿肌對硝普鈉敏感性較彊[最大舒張率：(50.6±2.1)% 和(67.9±4.1)%比(25.3±5.0)%,P<0.01],對Y-27632的敏感性較弱[(35.8±2.5)% 和(20.2±2.3)%比(71.6±2.8)%,P<0.01],組織cGMP含量較高[(20.6±4.1) fmol/mg和(29.4±4.3) fmol/mg比(12.9±2.1) fmol/mg,P<0.01];且每日灌胃組更為明顯(P<0.01).結論 高血壓模型大鼠膀胱逼尿肌存在不穩定收縮,5型燐痠二酯酶抑製劑能有效治療不穩定膀胱,且持續每日榦預效果更佳.5型燐痠二酯酶抑製劑改善膀胱逼尿肌不穩定收縮可能與cGMP介導的蛋白激酶G-RhoA/Rho激酶途徑有關.
목적 탐토5형린산이지매억제제대불은정방광적작용급가능도경.방법 성년자발성고혈압모형SD웅성대서24지,수궤수자표법분위매일관위조、간단관위조화공백조,매조8지,매일관위조：매일벌지나비(10mg·kg-1·d-1)관위;간단관위조：매격3 d벌지나비(10 mg·kg-1·d-1)관위;공백조：매일생리염수관위.령이8지성년웅성SD대서위대조조,행매일생리염수관위.2주후4조분별행방광뇨동역학검사.각취4조대서방광핍뇨기분위2빈,용우관찰예수축후초보납、Rho격매억제제Y-27632대대서방광핍뇨기서장작용적영향급용매련면역법측정조직중배린산조감(cGMP)함량.결과 공백조방광배뇨간격시간급방광용량균소우대조조[(409±36)s비(568±60)s;(284±25) μl 비 (395±42)μl,균P<0.01]、저뇨기방광수축차수대우대조조[(2.03±0.49) 차/min비(1.07±0.30)차/min,P<0.01];간단급매일관위조상술지표[(486±53)s 화 (564±44)s;(337±37)μl 화(392±30) μl;(1.82±0.32 )차/min화 (0.52±0.23) 차/min]교공백조명현개선(P<0.05);차매일관위조작용경위현저(P<0.01).간단급매일관위조여공백조비교,방광핍뇨기대초보납민감성교강[최대서장솔：(50.6±2.1)% 화(67.9±4.1)%비(25.3±5.0)%,P<0.01],대Y-27632적민감성교약[(35.8±2.5)% 화(20.2±2.3)%비(71.6±2.8)%,P<0.01],조직cGMP함량교고[(20.6±4.1) fmol/mg화(29.4±4.3) fmol/mg비(12.9±2.1) fmol/mg,P<0.01];차매일관위조경위명현(P<0.01).결론 고혈압모형대서방광핍뇨기존재불은정수축,5형린산이지매억제제능유효치료불은정방광,차지속매일간예효과경가.5형린산이지매억제제개선방광핍뇨기불은정수축가능여cGMP개도적단백격매G-RhoA/Rho격매도경유관.
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.
