利用小窝蛋白-1基因敲除小鼠研究衰老膀胱中逼尿肌收缩功能受损及毒蕈碱活性紊乱的情况。

Using caveolin-1 knockout mouse to study impaired detrusor contractility and disrupted muscarinic activity in the aging bladder.

作者信息

Lai H Henry, Boone Timothy B, Thompson Timothy C, Smith Christopher P, Somogyi George T

机构信息

Neurourology Laboratory, Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.

出版信息

Urology. 2007 Feb;69(2):407-11. doi: 10.1016/j.urology.2006.12.018.

DOI:10.1016/j.urology.2006.12.018

PMID:17320698

Abstract

OBJECTIVES

The caveolin-1 knockout mouse has been proposed as an animal model to study impaired bladder contractility and detrusor overactivity. This study investigated the effects of aging on detrusor contraction in wild type and caveolin-1 knockout mice.

METHODS

Young (3-month-old) and old (1-year-old) male caveolin-1 knockout mice and their age-matched male wild type littermates (controls) were used. Longitudinal bladder strips were stimulated electrically (20 Hz) and pharmacologically using 1 to 10 microM carbachol (a nonsubtype selective cholinergic receptor agonist), 10 microM alpha,beta-methylene adenosine triphosphate (a purinergic receptor agonist), and 100 mM potassium (a depolarizing agent). Isometric bladder strip contractions were compared between the young wild type and knockout groups and between the old wild type and knockout groups.

RESULTS

The bladder strips from the 1-year-old knockout mice exhibited a 40% to 42% decrease in electrical neural contractions and carbachol-evoked contractions compared with the 1-year-old wild type controls (P <0.05). Even though the bladder strips from the 3-month-old knockout mice demonstrated a smaller decrease (29% to 32%) in electrical neural contractions and carbachol-evoked contractions compared with their age-matched controls, the trend did not reach statistical significance (P >0.05). The postjunctional cholinergic pathway was specifically disrupted in caveolin-1 knockout animals because no difference was found in contractility between the knockout and wild type mice (young or old) when the bladders were stimulated by alpha,beta-methylene adenosine triphosphate or potassium. The differences in cholinergic contractility between the knockout and wild type mice became significantly greater as the animals aged from 3 months old (young bladders) to 1 year old (aged bladders).

CONCLUSIONS

The male caveolin-1 knockout mouse provides a much-needed animal model for the study of impaired detrusor contractility in the aging bladder.

摘要

目的

有人提出将小窝蛋白-1基因敲除小鼠作为研究膀胱收缩功能受损和逼尿肌过度活动的动物模型。本研究调查了衰老对野生型和小窝蛋白-1基因敲除小鼠逼尿肌收缩的影响。

方法

使用年轻（3个月大）和年老（1岁）的雄性小窝蛋白-1基因敲除小鼠及其年龄匹配的雄性野生型同窝小鼠（对照）。纵向膀胱条用电刺激（20Hz），并使用1至10微摩尔卡巴胆碱（一种非亚型选择性胆碱能受体激动剂）、10微摩尔α,β-亚甲基三磷酸腺苷（一种嘌呤能受体激动剂）和100毫摩尔钾（一种去极化剂）进行药理学刺激。比较年轻野生型和基因敲除组之间以及年老野生型和基因敲除组之间等长膀胱条收缩情况。

结果

与1岁野生型对照相比，1岁基因敲除小鼠的膀胱条电神经收缩和卡巴胆碱诱发的收缩减少了40%至42%（P<0.05）。尽管与年龄匹配的对照相比，3个月大基因敲除小鼠的膀胱条电神经收缩和卡巴胆碱诱发的收缩减少幅度较小（29%至32%），但该趋势未达到统计学显著性（P>0.05）。在小窝蛋白-1基因敲除动物中，节后胆碱能途径被特异性破坏，因为当膀胱用α,β-亚甲基三磷酸腺苷或钾刺激时，基因敲除小鼠和野生型小鼠（年轻或年老）之间的收缩性没有差异。随着动物从3个月大（年轻膀胱）到1岁（年老膀胱），基因敲除小鼠和野生型小鼠之间胆碱能收缩性的差异变得更加显著。