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BENIGN BLADDER DISEASE AND MITOCHONDRIAL FUNCTION

良性膀胱疾病和线粒体功能

基本信息

批准号：
2905621
负责人：
ALAN PAUL HUDSON
金额：
$ 13.53万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-07-26 至 2001-06-30
项目状态：
已结题

项目摘要

DESCRIPTION: Partial bladder obstruction secondary to benign prostatic hyperplasia is associated with increased bladder mass, alterations in bladder capacity, in bladder compliance and in in vitro responses to pharmacological stimulations. In the rabbit, the obstruction-induced changes in the bladder mass and function stabilized after 14 days. In the compensated period, alterations in biochemical parameters such as lactic acid, CO2 production and pyruvate metabolism and Krebs cycle enzyme activities indicate that mitochondrial energy production is affected. While physiological and biochemical changes of the obstructed bladder have been characterized, few studies of molecular mechanisms underlying these alterations have been attempted. The investigators have shown that in the first 14 days post obstruction, the relative number of copies of the mitochondrial genome decreases by 10-fold in the rabbit bladder; while TCA cycle enzymes decline in activity, cytochrome oxidase does not. Furthermore, although mitochondrial genome copy number decreases, mitochondrial transcript remains near normal, suggesting an upregulation of mitochondrial transcription in the compensated period. In the present proposal, the investigators plan to define alterations in expression for mitochondrial and nuclear genes during the compensated and decompensated periods after partial obstruction in rabbit. They also plan to correlate the molecular findings with urodynamic status, bladder mass, and the contractile responses to autonomic agonists, field stimulation and KCl. These studies will increase understanding of the molecular basis for bladder dysfunction after obstruction and may provide useful information for designing new therapeutic tools.

描述：继发于良性前列腺的部分膀胱梗阻增生与膀胱重量增加、膀胱容量，膀胱顺应性和体外反应，药理刺激。在家兔中，膀胱质量和功能的变化在14天后稳定。在代偿期，生化参数的改变，如乳酸酸、CO2产生和丙酮酸代谢以及克雷布斯循环酶活性表明线粒体能量产生受到影响。而梗阻膀胱的生理和生化变化已经被特征，很少有研究的分子机制，这些已经尝试过改变。研究人员发现，在阻塞后的第14天，线粒体基因组在兔膀胱中减少了10倍;而TCA 循环酶的活性下降，细胞色素氧化酶不。此外，虽然线粒体基因组拷贝数减少，线粒体转录物保持接近正常，表明线粒体转录的变化。本建议，调查人员计划定义表达的改变，线粒体和核基因在代偿和失代偿期间家兔部分梗阻后的时间。他们还计划将尿流动力学状态、膀胱质量和对自主激动剂、场刺激和KCl的收缩反应。这些研究将增加对膀胱癌的分子基础的理解，梗阻后的功能障碍，并可能提供有用的信息，设计新的治疗工具