Improvement by Phytotherapeutic Agent of Detrusor Overactivity, Down-Regulation of Pharmacological Receptors and Urinary Cytokines in Rats with Cyclophosphamide Induced Cystitis
Improvement by Phytotherapeutic Agent of Detrusor Overactivity, Down-Regulation of Pharmacological Receptors and Urinary Cytokines in Rats with Cyclophosphamide Induced Cystitis
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DOI：
10.1016/j.juro.2012.09.054
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发表时间：
2013-03-01
影响因子：
6.6
通讯作者：
Yamada, Shizuo
中科院分区：
文献类型：
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作者：
Nasrin, Sweety;Masuda, Eiji;Yamada, Shizuo
目的：我们研究了植物治疗剂 Eviprostat(R) 对环磷酰胺诱发的膀胱炎大鼠的尿动力学参数、膀胱毒蕈碱和嘌呤能受体以及尿细胞因子的药理作用。材料和方法：对环磷酰胺（150 mg/kg 腹腔注射）治疗的大鼠的尿动力学参数进行了研究 通过膀胱测压法测量。分别使用[N-甲基-H-3]东莨菪碱甲基氯化物和[H-3]αβ-MeATP通过放射性受体测定来测量膀胱和其他组织中的毒蕈碱和嘌呤能受体。采用酶联免疫试剂盒测定尿细胞因子白细胞介素1β、6和17。口服依维前列他（36 mg/kg，每天两次，持续 7 天）。 结果：膀胱测压显示，与假治疗组大鼠相比，环磷酰胺组的排尿间隔和排尿量显着减少，而排尿频率、基础压力和排尿后残余尿量显着增加。环磷酰胺治疗大鼠重复口服依维前列素可显着增加排尿间隔和排尿量，并降低排尿频率、基础压和排尿后残余尿量。与假处理组相比，环磷酰胺膀胱中[N-甲基-3H]东莨菪碱甲基氯化物和[H-3]αβ-MeATP的最大结合位点数量显着减少。重复依前列醇治疗可显着减弱这种下降。 Eviprostat 也能有效减弱环磷酰胺治疗大鼠尿细胞因子水平的升高。结论：重复 Eviprostat 治疗可显着改善环磷酰胺诱发膀胱炎大鼠的逼尿肌过度活动，下调膀胱药理学受体的表达，并增加尿细胞因子水平。因此，Eviprostat 可能是一种药理学上有用的膀胱炎植物治疗剂。
Purpose: We characterized pharmacological effects of the phytotherapeutic agent Eviprostat(R) on urodynamic parameters, bladder muscarinic and purinergic receptors, and urinary cytokines in rats with cyclophosphamide induced cystitis.Materials and Methods: Urodynamic parameters in cyclophosphamide (150 mg/kg intraperitoneally) treated rats were measured by a cystometric method. Muscarinic and purinergic receptors in the bladder and other tissues were measured by radioreceptor assays using [N-methyl-H-3]scopolamine methyl chloride and [H-3]alpha beta-MeATP, respectively. The urinary cytokines interleukin-1 beta, 6 and 17 were measured with enzyme-linked immunoassay kits. Eviprostat (36 mg/kg per day twice daily for 7 days) was orally administered.Results: On cystometry the micturition interval and micturition volume were significantly decreased in cyclophosphamide vs sham treated rats, while micturition frequency, basal pressure and post-void residual urine volume were significantly increased. Repeat oral administration of Eviprostat in cyclophosphamide treated rats significantly increased the micturition interval and micturition volume, and decreased micturition frequency, basal pressure and post-void residual urine volume. The maximal number of binding sites for [N-methyl-3H] scopolamine methyl chloride and [H-3]alpha beta-MeATP was significantly decreased in the bladder of cyclophosphamide vs sham treated rats. Such decreases were significantly attenuated by repeat Eviprostat treatment. Increased urinary cytokine levels in cyclophosphamide treated rats were also effectively attenuated by Eviprostat.Conclusions: Repeat Eviprostat treatment significantly improved detrusor over-activity, down-regulated the expression of bladder pharmacological receptors and increased urinary cytokine levels in rats with cyclophosphamide induced cystitis. Therefore, Eviprostat may be a pharmacologically useful phytotherapeutic agent for cystitis.