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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:2μg组胺(10μg/mL)治疗组、1.1μg 5-羟色胺(5.5μg/mL)治疗组、2μg组胺与1.1μg 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。
Objective To explore the effect of low dose histamine and serotonin on bladder function in rats with overactive bladder (OAB). Methods 40 SD female rats were subjected to incomplete bladder outlet obstruction (PBOO) to simulate the clinical urodynamic changes of OAB. After operation, the rats were randomly divided into 4 groups: 2μg histamine (10μg / mL), 1.1 μg serotonin (5.5μg / mL) treatment group, 2μg histamine and 1.1μg serotonin combination group and model control group. Another 10 female SD rats were sham-operated and treated with saline. Drug and saline treatment began on the 10th postoperative day, the method of administration was subcutaneous injection twice daily for 1 week. The urodynamic parameters of urinary storage period and urination period of rats in each group were recorded by measuring the pressure of the bladder under awake condition. The urinary bladder tissues were weighed and analyzed histologically after completion. One-way ANOVA and Tukey’s multiple post hoc multiple comparison methods were used to analyze the quantitative data between groups. Results Compared with the sham-operation group, the frequency and amplitude of detrusor instability in model control group, histamine treatment group, serotonin treatment group and combination of histamine and serotonin group rats, amplitude, maximum bladder capacity, Urine contraction interval, residual urine volume and bladder mass increased (P <0.05). Compared with the model control group, the amplitude of micturition contraction increased only in the combination group, and the amplitude of unstable contraction and residual urine volume decreased (P <0.05). Histological analysis showed that the detrusor fibers of the rats treated with combination therapy and histamine alone were continuous and closely arranged. Conclusions Combined administration of low doses of histamine and serotonin can effectively improve the stability of urinary bladder function in OAB rats and improve the emptying efficiency of bladder, which may provide a new idea for clinical OAB treatment.