5-羟色胺1A受体激动剂改善糖尿病大鼠排尿功能障碍的实验研究  

Experimental study of 5-hydroxytryptamine 1A receptor agonist to improve the voiding dysfunction in diabetic rats

作　　者：陈加生[1] 吴刚[1] 谷宝军[1] 

机构地区：[1]上海交通大学附属第六人民医院泌尿外科,200233

出　　处：《中华泌尿外科杂志》2014年第4期301-305,共5页Chinese Journal of Urology

基　　金：国家自然科学基金（30872568）;上海市科学技术委员会科研计划项目（09QH1402000）

摘　　要：目的 研究5-羟色胺1A（5-HT1A）受体激动剂对糖尿病大鼠排尿障碍的改善作用.方法 SD雌性大鼠14只,体质量250～ 275 g.采用随机数字表法随机分成2组：实验组7只腹腔注射链脲霉素65 mg/kg建立糖尿病大鼠模型,对照组7只.8周后乌拉坦1.3 g/kg麻醉下,2组大鼠颈静脉和膀胱内置管,连接压力感受器,记录排尿量、残余尿量、膀胱容量和尿道外括约肌的肌电活动.静脉注入5-HT1A受体激动剂8-羟基-丙胺-四氢萘（8-OH-DPAT,0.003～ 1.000 mg/kg）,得到剂量-效应曲线后再给予5-HT1A受体抑制剂WAY-100635（0.300 mg/kg）.观察比较2组大鼠用药前后尿动力学指标的变化. 结果 糖尿病大鼠膀胱容量、残余尿量高于对照组大鼠,排尿效率下降.随着8-OH-DPAT（0.003～ 1.000 mg/kg）剂量增加,糖尿病大鼠排尿量从（2.15±0.49） ml增至（2.85±0.21） ml,残余尿量从（3.40±0.74） ml降至（1.82±.0.48） ml,排尿效率从（39.0±9.3）％增至（61.6±6.9）％.对照组大鼠用药前后排尿情况变化差异无统计学意义（P＞0.05）.肌电图显示8-OH-DPAT能改善糖尿病大鼠受损的尿道外括约肌高频舒张收缩功能,对于对照组大鼠也有增强作用.而WAY-100635能逆转8-OH-DPAT的效应. 结论 糖尿病大鼠尿道外括约肌高频舒张收缩活动减弱,排尿效率下降.5-HT1A受体激动剂8-OH-DPAT可以部分恢复糖尿病大鼠尿道外括约肌协调性松弛,从而提高排尿效率,改善排尿障碍.Objective To investigate the effect of 5-hydroxytryptamine 1A （5-HT1A） receptor agonists to improve micturition function in rats with diabetes mellitus （DM）.Methods Fourteen female SD rats with the weight of 250 to 275 g were used.Seven rats were in the DM model group with intraperitoneal injection streptozotocin （STZ,65 mg/kg）.Rats in the control group and DM group were anesthetized with urethane （1.3 g/kg） 8 weeks later.A polyethylene （PE）-50 catheter were placed in the left jugular vein for intravenous drug administration.A PE-90 catheter was inserted into the bladder,with the other end connected to a syringe pump for continuous infusion of saline and a pressure transducer for intravesical pressure monitor.Dose-response curves for 8-OH-DPAT were followed by WAY-100635 test.The capacity,residual volume,micturition volume,and EUS-EMG were measured.Results Compared to normal control,DM rats had a higher bladder capacity,residual volume,and a lower voiding efficiency.With increasing dose of 8-OH-DPAT （0.003-1.000 mg/kg,i.v.）,the micturition volume increased from （2.15±0.49） ml to （2.85±0.21） ml,the residual volume decreased from （3.40±0.74）ml to （1.82±0.48） ml and voiding efficiency changed from （39.0±9.3）％ to （61.6±6.9）％.Control rats showed little change in cystometic variable.During the micturition,there was a dose-dependent increased phasic EUS activity correlated with the improved voiding efficiency.WAY-100635 （0.300 mg/kg,i.v.） reversed the 8-OH-DPAT-induced changes.Conclusions Both the bladder voiding efficiency and the periodic EUS activity decrease in DM rats.5-HT1A receptor agonist could promote periodic EUS activity and improve voiding efficiency.

关 键 词：大鼠 糖尿病 排尿 受体 血清素 5-HT1A 血清素激动药 

分 类 号：R587.1[医药卫生—内分泌]