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兔部分梗阻两周后他地那治疗的有益效果。

Beneficial effects of Tadenan therapy after two weeks of partial obstruction in the rabbit.

作者信息

Levin R M, Das A K, Haugaard N, Novitsky Y, Horan P, Leggett R E, Riffaud J P, Longhurst P A

机构信息

Albany College of Pharmacy, New York 12208-3492, USA.

出版信息

Neurourol Urodyn. 1997;16(6):583-99. doi: 10.1002/(sici)1520-6777(1997)16:6<583::aid-nau8>3.0.co;2-a.

Abstract

Tadenan (Debat Laboratories, France) is a plant extract used in Europe for the treatment of micturition disorders associated with benign prostatic hypertrophy (BPH). Prior studies demonstrated that pretreatment of rabbits with Tadenan significantly reduced the contractile dysfunction observed after 2 weeks of partial outlet obstruction. The specific aim of the present study was to determine the effect of Tadenan therapy following the creation of partial outlet obstruction. Two sets of experiments were performed: one with mild and the other with severe outlet obstruction. For both sets of experiments, male New Zealand rabbits (3-5 kg) were separated into 3 groups of 5 rabbits each. Each rabbit in groups 1 and 2 was obstructed using standard methodology. Rabbits in group 3 served as controls and did not receive any surgery. After 2 weeks, each rabbit in group 1 received Tadenan orally at 100 mg/kg/day for 3 weeks; each rabbit in group 2 received vehicle (peanut oil). After 3 weeks of treatment (5 weeks after partial outlet obstruction), rabbits were anesthetized and cystometries were performed. Immediately after cystometry, the rabbits were euthanized, the bladder rapidly removed, and 4 longitudinal strips prepared and mounted in individual baths for contractile studies. The contractile responses to field stimulation, carbachol, adenosine-5'-triphosphate (ATP), and potassium chloride (KCl) were determined, as follows: (1) Bladder mass approximately doubled in the mildly obstructed groups. Bladder mass increased significantly (3-5-fold) in the severely obstructed groups. (2) Cystometrograms from the mildly obstructed rabbits treated with peanut oil showed low compliance, whereas those of the mildly obstructed rabbits treated with Tadenan showed normal compliance. The cystometrograms of all severely obstructed rabbits showed low compliance. (3) Mild obstruction caused small but significant decreases in the contractile response to field stimulation that were reversed by Tadenan treatment. No changes were noted in response to bethanechol, ATP, and KCl stimulation. (4) Severe obstruction caused significant decreases in the response of bladder strips to field stimulation and bethanechol. Following Tadenan therapy, there was a significant improvement in the response to high-frequency field stimulation and a substantial improvement in the response to bethanechol (response equal to control). No changes were noted in response to ATP and KCl stimulation. In conclusion, Tadenan treatment reversed the bladder dysfunctions induced by mild partial outlet obstruction, and resulted in improved bladder function in the severe model of outlet obstruction. These studies are consistent with previous studies showing that Tadenan pretreatment protects the bladder against the development of contractile dysfunctions.

摘要

他达那(法国德巴特实验室)是一种植物提取物,在欧洲用于治疗与良性前列腺增生(BPH)相关的排尿障碍。先前的研究表明,用他达那对兔子进行预处理可显著降低部分尿道梗阻2周后观察到的收缩功能障碍。本研究的具体目的是确定部分尿道梗阻形成后他达那治疗的效果。进行了两组实验:一组为轻度梗阻,另一组为重度梗阻。对于这两组实验,将雄性新西兰兔(3 - 5千克)分为3组,每组5只兔子。第1组和第2组的每只兔子都采用标准方法进行梗阻。第3组兔子作为对照,未接受任何手术。2周后,第1组的每只兔子每天口服100毫克/千克他达那,持续3周;第2组的每只兔子接受赋形剂(花生油)。治疗3周后(部分尿道梗阻5周后),将兔子麻醉并进行膀胱测压。膀胱测压后立即对兔子实施安乐死,迅速取出膀胱,制备4条纵向肌条并安装在单独的浴槽中进行收缩研究。测定了对场刺激、卡巴胆碱、三磷酸腺苷(ATP)和氯化钾(KCl)的收缩反应,结果如下:(1)轻度梗阻组的膀胱重量大约增加了一倍。重度梗阻组的膀胱重量显著增加(3 - 5倍)。(2)用花生油治疗的轻度梗阻兔子的膀胱测压图显示顺应性低,而用他达那治疗的轻度梗阻兔子的膀胱测压图显示顺应性正常。所有重度梗阻兔子的膀胱测压图均显示顺应性低。(3)轻度梗阻导致对场刺激的收缩反应出现小幅度但显著的降低,并被他达那治疗逆转。对氨甲酰甲胆碱、ATP和KCl刺激的反应未观察到变化。(4)重度梗阻导致膀胱肌条对场刺激和氨甲酰甲胆碱的反应显著降低。他达那治疗后,对高频场刺激的反应有显著改善,对氨甲酰甲胆碱的反应有实质性改善(反应与对照相当)。对ATP和KCl刺激的反应未观察到变化。总之,他达那治疗逆转了轻度部分尿道梗阻引起的膀胱功能障碍,并在重度尿道梗阻模型中改善了膀胱功能。这些研究与先前的研究一致,表明他达那预处理可保护膀胱免受收缩功能障碍的影响。

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