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组胺与5-羟色胺对膀胱过度活动症大鼠膀胱功能的影响
宋奇翔,叶宸,谭海颂,张振声,李惠珍,许传亮,孙颖浩*
0
(第二军医大学长海医院泌尿外科, 上海 200433
*通信作者)
摘要:
目的 探索低剂量的组胺与5-羟色胺对膀胱过度活动症(OAB)大鼠膀胱功能的影响。方法 对40只SD雌性大鼠实施膀胱出口不全梗阻手术(PBOO),模拟OAB的临床尿动力学改变,术后将大鼠随机分为4组:2 μg组胺(10 μg/mL)治疗组、1.1 μg 5-羟色胺(5.5 μg/mL)治疗组、2 μg组胺与1.1 μg 5-羟色胺联合用药组及模型对照组。另外10只SD雌性大鼠予以假手术并用生理盐水处理。药物及生理盐水治疗均开始于术后第10天,给药方法为皮下注射,每日2次,持续1周。通过清醒状态下的膀胱压力测定记录各组大鼠储尿期与排尿期的尿动力学指标,完毕后收取膀胱组织称量并进行组织学分析。采用单因素方差分析和Tukey事后多重比较方法对组间的定量数据进行统计学分析。结果 与假手术组相比,模型对照组、组胺治疗组、5-羟色胺治疗组及组胺与5-羟色胺联合用药组大鼠的逼尿肌不稳定收缩的频率、振幅、膀胱最大容量、排尿收缩的间隔时间、残余尿量以及膀胱质量均有提升(P<0.05)。与模型对照组相比较,仅联合用药组大鼠的排尿收缩振幅有提升,不稳定收缩的振幅与残余尿量均降低(P<0.05)。组织学分析表明联合用药与单用组胺治疗组大鼠逼尿肌纤维连续且排列紧密。结论 联合应用低剂量的组胺与5-羟色胺可有效改善OAB大鼠储尿期膀胱功能的稳定性,并提高膀胱的排空效率,可为临床OAB治疗提供一种新的思路。
关键词:  过度活动性膀胱  下尿路症状  逼尿肌不稳定收缩  膀胱组织学  膀胱内测压  组胺  血清素
DOI:10.16781/j.0258-879x.2017.01.0015
投稿时间:2016-05-18修订日期:2016-11-28
基金项目:国家自然科学基金青年科学基金(81500579).
Effects of histamine and serotonin on bladder function of overactive bladder rats
SONG Qi-xiang,YE Chen,TAN Hai-song,ZHANG Zhen-sheng,LI Hui-zhen,XU Chuan-liang,SUN Ying-hao*
(Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
*Corresponding author)
Abstract:
Objective To study the effects of low-dose histamine and serotonin on bladder function of overactive bladder (OAB) rats. Methods OAB model of female SD rat was successfully established by partial bladder outlet obstruction (PBOO) to simulate clinical OAB urodynamic changes. Forty OAB rats were randomly divided into four groups: PBOO+histamine group (2 μg histamine), PBOO+serotonin group (1.1 μg serotonin), PBOO+combination group (combined treatment of 2 μg histamine and 1.1 μg serotonin) and PBOO+normal saline (NS) group. Ten SD rats undergoing sham PBOO and receiving normal saline served as sham group. All subcutaneous injections began at 10 days after PBOO surgery (twice daily for one week). The urodynamic indexes of rats were recorded under conscious state by bladder pressure measurement during urinary storage and micturition, and then bladder tissues were collected, weighted and stained with Masson's trichrome for histological assessment. The quantitative data of groups were compared and analyzed using one-way ANOVA followed by a Tukey's post hoc test. Results Compared with sham group, the other four groups had significantly increased frequency and amplitude of non-voiding contraction, maximum bladder capacity, interval of micturition contraction, residual urine volume and bladder weight (P<0.05). Compared with PBOO+NS group, the amplitude of micturition contraction was significantly increased, the frequency of non-voiding contraction and residual urine volume were significantly reduced in PBOO+combination group (P<0.05). Moreover, histological analysis showed that detrusor arrangement was continuous and close in PBOO+combination and PBOO+histamine groups. Conclusion Combined use of low-dose histamine and serotonin can improve the stability of bladder function during urinary storage and increase the empty efficiency of bladder, which may provide a new way for clinical treatment of OAB.
Key words:  overactive urinary bladder  lower urinary tract symptoms  instable detrusor constriction  bladder histology  bladder pressure measurement  histamine  serotonin