米拉贝隆联合电针对膀胱过度活动症大鼠尿动力学的影响及机制研究

Effects and mechanisms of mirabegron combined with electroacupuncture on urodynamics in rats with overactive bladder

  • 摘要:
    目的 探讨米拉贝隆联合电针通过调控胰岛素受体底物(IRS)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/内皮型一氧化氮合酶(eNOS)信号通路对膀胱过度活动症(OAB)大鼠尿动力学指标的影响。
    方法 选取60只雌性SD大鼠作为研究对象, 采用随机数字表法分为对照组、模型组、米拉贝隆组、电针组、米拉贝隆+电针组,每组12只。除对照组外,其余各组采用膀胱出口梗阻法建立OAB大鼠模型。米拉贝隆组灌胃8 mg/kg米拉贝隆混悬液,电针组每次电针刺激5 min, 米拉贝隆+电针组灌胃米拉贝隆混悬液的同时接受电针刺激,对照组、模型组和电针组灌胃等量生理盐水, 1次/d, 连续7 d。检测各组大鼠尿动力学指标(基础排尿压、排尿压峰值、排尿间隔时间、剩余尿量); 使用激光散斑成像仪检测膀胱血流量后,称取大鼠膀胱组织湿质量并计算膀胱指数; 采用酶联免疫吸附测定(ELISA)检测尿液神经生长因子(NGF)及膀胱组织白细胞介素-1β(IL-1β)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量; 采用蛋白质印迹法(Western blot)检测膀胱组织磷酸化(p)-IRS1、p-PI3K、p-AKT、p-eNOS表达水平。
    结果 与模型组相比,米拉贝隆组、电针组、米拉贝隆+电针组的基础排尿压、排尿压峰值和膀胱指数均降低,剩余尿量均减少,排尿间隔时间均延长,膀胱血流量均增加,膀胱组织SOD含量均升高,尿液NGF含量和膀胱组织IL-1β、MDA含量均降低, p-IRS1、p-PI3K、p-AKT、p-eNOS表达水平均升高,差异有统计学意义(P < 0.05或P < 0.01); 米拉贝隆+电针组上述指标结果均优于米拉贝隆组、电针组,差异有统计学意义(P < 0.05或P < 0.01)。
    结论 米拉贝隆联合电针比二者单独使用更能改善OAB大鼠的尿动力学指标,其机制可能与激活IRS/PI3K/AKT/eNOS信号通路有关。

     

    Abstract:
    Objective To investigate the effects of mirabegron combined with electroacupuncture on urodynamic parameters in rats with overactive bladder (OAB) by regulating the insulin receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) signaling pathway.
    Methods Sixty female SD rats were selected as the study subjects and randomly divided into control group, model group, mirabegron group, electroacupuncture group, and mirabegron+electroacupuncture group using a random number table method, with 12 rats in each group. Except for the control group, the other groups were used to establish OAB rat models by the bladder outlet obstruction method. The mirabegron group received intragastric administration of 8 mg/kg mirabegron suspension. The electroacupuncture group received electroacupuncture stimulation for 5 min each time. The mirabegron+electroacupuncture group received intragastric administration of mirabegron suspension while undergoing electroacupuncture stimulation. The control group, the model group, and the electroacupuncture group received an equal volume of normal saline intragastrically once a day for 7 consecutive days. Urodynamic parameters (basal micturition pressure, peak micturition pressure, micturition interval, and residual urine volume) were measured in each group. After measuring bladder blood flow using a laser speckle imaging instrument, the wet weight of the rat bladder tissue was weighed, and the bladder index was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of urinary nerve growth factor (NGF), and interleukin-1β (IL-1β), malondialdehyde (MDA), and superoxide dismutase (SOD) in bladder tissue. Western blot was used to detect the expression levels of phosphorylated (p)-IRS1, p-PI3K, p-AKT and p-eNOS in bladder tissue.
    Results Compared with the model group, the basal micturition pressure, peak micturition pressure, and bladder index were all decreased, the residual urine volume was reduced, the micturition interval was prolonged, the bladder blood flow was increased, the SOD content in bladder tissue was increased, the NGF content in urine and the IL-1β and MDA contents in bladder tissue were decreased, and the expression levels of p-IRS1, p-PI3K, p-AKT and p-eNOS were increased in the mirabegron group, the electroacupuncture group, and the mirabegron+electroacupuncture group, with statistically significant differences (P < 0.05 or P < 0.01). The results of the above indicators in the mirabegron+electroacupuncture group were all better than those in the mirabegron group and the electroacupuncture group, with statistically significant differences (P < 0.05 or P < 0.01).
    Conclusion Mirabegron combined with electroacupuncture can improve urodynamic parameters in OAB rats than used alone, and its mechanism may be related to the activation of the IRS/PI3K/AKT/eNOS signaling pathway.

     

/

返回文章
返回