红霉素对大鼠逼尿肌收缩的直接抑制作用。

Direct inhibition of rat detrusor muscle contraction by erythromycin.

作者信息

England Roland C D, Norman Robert I, Elliott Ruth A

机构信息

Department of Urology, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, United Kingdom.

出版信息

Neurourol Urodyn. 2004;23(3):273-9. doi: 10.1002/nau.20019.

DOI:10.1002/nau.20019

PMID:15098226

Abstract

PURPOSE

Detrusor instability is a common problem in the elderly, which is usually treated with anti-cholinergic medication. This study investigates the effect of erythromycin on rat detrusor muscle contractile response to characterise its potential as an alternative inhibitor of bladder muscle contraction.

MATERIALS AND METHODS

Strips of rat detrusor muscle were suspended in a perfusion organ bath. The contractile response to direct muscle stimulation, electrical field stimulation (EFS, 0.5-60 Hz), carbachol (10(-5) M), and potassium (10-80 x 10(-3) M) were determined before and after the addition of erythromycin (10(-4)-10(-3) M). The contractile response to carbachol (10(-5) M) in the presence of nifedipine (10(-8) or 10(-6) M) or in calcium-free Kreb's solution was also determined in the absence and presence of erythromycin.

RESULTS

Erythromycin 5 x 10(-4) M inhibited the maximum contractile response to EFS, carbachol, and potassium by 38% (P < 0.01), 62% (P < 0.001), and 17% (P < 0.05), respectively, but did not significantly reduce the response to direct muscle stimulation. The atropine-resistant component of EFS-evoked contraction was inhibited by 19.5% (P < 0.01) in the presence of erythromycin. In calcium-free Krebs solution, the maximum contractile response to carbachol was reduced by 42% of control (P < 0.0001) and nifedipine 10(-8) M had no additional effect. When erythromycin 5 x 10(-4) M was added together with nifedipine 10(-8) M, the response to carbachol was inhibited by a further 25% (P < 0.005).

CONCLUSIONS

Erythromycin inhibits rat detrusor muscle contraction through the inhibition of calcium influx and the modulation of intracellular calcium movement.

摘要

目的

逼尿肌不稳定是老年人常见的问题，通常用抗胆碱能药物治疗。本研究调查红霉素对大鼠逼尿肌收缩反应的影响，以确定其作为膀胱肌肉收缩替代抑制剂的潜力。

材料与方法

将大鼠逼尿肌条悬于灌注器官浴槽中。在加入红霉素（10⁻⁴ - 10⁻³ M）之前和之后，测定对直接肌肉刺激、电场刺激（EFS，0.5 - 60 Hz）、卡巴胆碱（10⁻⁵ M）和钾（10 - 80×10⁻³ M）的收缩反应。还在有无红霉素的情况下，测定在硝苯地平（10⁻⁸ 或 10⁻⁶ M）存在时或在无钙的克雷布斯溶液中对卡巴胆碱（10⁻⁵ M）的收缩反应。

结果

5×10⁻⁴ M 的红霉素分别使对 EFS、卡巴胆碱和钾的最大收缩反应抑制 38%（P < 0.01）、62%（P < 0.001）和 17%（P < 0.05），但对直接肌肉刺激的反应无显著降低。在红霉素存在时，EFS 诱发收缩的抗阿托品成分被抑制 19.5%（P < 0.01）。在无钙的克雷布斯溶液中，对卡巴胆碱的最大收缩反应比对照降低 42%（P < 0.0001），10⁻⁸ M 的硝苯地平无额外作用。当 5×10⁻⁴ M 的红霉素与 10⁻⁸ M 的硝苯地平一起加入时，对卡巴胆碱的反应进一步被抑制 25%（P < 0.005）。