年龄对雄性大鼠膀胱中过氧化氢介导的收缩损伤的影响。

Effect of age on hydrogen peroxide mediated contraction damage in the male rat bladder.

作者信息

Aikawa Ken, Leggett Robert E, Levin Robert M

机构信息

Division of Basic and Pharmaceutical Sciences, Albany College of Pharmacy, 106 New Scotland Avenue, Albany, NY 12208, USA.

出版信息

J Urol. 2003 Nov;170(5):2082-5. doi: 10.1097/01.ju.0000081461.73156.48.

DOI:10.1097/01.ju.0000081461.73156.48

PMID:14532858

Abstract

PURPOSE

Recent studies introduced the concept that reactive oxygen species (ROS) may be a major factor in the progressive deterioration of bladder function induced by benign prostatic hyperplasia in men and following partial outlet obstruction in animals. We determined whether bladder contraction sensitivity to ROS changes with aging. Using H2O2 to simulate ROS damage we compared the sensitivity of the contractile responses of bladder smooth muscle isolated from young and elderly rats to H2O2.

MATERIALS AND METHODS

Male 3-month-old (young) and 12-month-old (elderly) Sprague-Dawley rats were used for this study with 24 per group. Each rat was anesthetized and the bladder was excised. Two longitudinal strips were cut from the bladder body. Each strip was placed in individual 15 ml baths containing oxygenated Tyrode's solution at 37C. Each strip was stimulated at 32 Hz for 20 seconds with pulses 1 millisecond in duration at 80 V. After electrical field stimulation (EFS) the response to 20 microM carbachol and 120 mM KCl was determined. The bath solution was then exchanged for H2O2 solutions of 6 different concentrations including 0%, 0.0625%, 0.125%, 0.25%, 0.5% and 1.0%. After 1 hour of exposure to H2O2 the tissues were washed free of H2O2, and the response to EFS, carbachol and KCl were measured again. At the end of the experiment the strips were weighed and frozen at -70C for malondialdehyde analysis.

RESULTS

The magnitude of the contractile responses of the young and elderly rats to all forms of stimulation were equal. Hydrogen peroxide caused a dose dependent decrease in the contractile responses of bladder strips to all forms of stimulation. Contractile responses to carbachol and KCl were more sensitive to H2O2 than to EFS. Contractile responses of bladder strips isolated from elderly rats were significantly more sensitive to H2O2 damage than strips isolated from young rats. Malondialdehyde generation of bladder strips isolated from elderly rats was significantly greater than those from young rats.

CONCLUSIONS

It is suggested that aging increases the sensitivity of detrusor contraction to oxidative damage.

摘要

目的

最近的研究提出了这样一个概念，即活性氧（ROS）可能是男性良性前列腺增生以及动物部分尿道梗阻后膀胱功能进行性恶化的主要因素。我们确定膀胱对ROS的收缩敏感性是否会随着衰老而变化。使用过氧化氢模拟ROS损伤，我们比较了从年轻和老年大鼠分离的膀胱平滑肌对过氧化氢的收缩反应敏感性。

材料与方法

本研究使用3个月大（年轻）和12个月大（老年）的雄性Sprague-Dawley大鼠，每组24只。每只大鼠麻醉后切除膀胱。从膀胱体切下两条纵向肌条。每条肌条置于单独的15毫升浴槽中，浴槽中含有37℃的含氧台氏液。每条肌条以80伏、持续时间1毫秒的脉冲在32赫兹下刺激20秒。电场刺激（EFS）后，测定对20微摩尔卡巴胆碱和120毫摩尔氯化钾的反应。然后将浴槽溶液换成6种不同浓度的过氧化氢溶液，浓度分别为零、0.0625%、0.125%、0.25%、0.5%和1.0%。暴露于过氧化氢1小时后，将组织冲洗以去除过氧化氢，然后再次测量对EFS、卡巴胆碱和氯化钾的反应。实验结束时，称取肌条重量并在-70℃冷冻以进行丙二醛分析。

结果

年轻和老年大鼠对所有形式刺激的收缩反应幅度相同。过氧化氢导致膀胱肌条对所有形式刺激的收缩反应呈剂量依赖性降低。对卡巴胆碱和氯化钾的收缩反应对过氧化氢比对EFS更敏感。从老年大鼠分离的膀胱肌条的收缩反应对过氧化氢损伤的敏感性明显高于从年轻大鼠分离的肌条。从老年大鼠分离的膀胱肌条产生的丙二醛明显多于年轻大鼠的。