BENIGN BLADDER DISEASE AND MITOCHONDRIAL FUNCTION

描述：良性前列腺继发部分性膀胱梗阻 增生症与膀胱质量增加有关，改变 膀胱容量、膀胱顺应性和体外反应 药理刺激。在兔体内，梗阻诱导 14天后膀胱质量和功能的变化趋于稳定。在 代偿期，乳酸等生化指标的变化 酸、二氧化碳产生和丙酮酸代谢与Krebs循环酶 活动表明线粒体的能量产生受到影响。而当 梗阻性膀胱的生理生化改变 其特点是，对其背后的分子机制研究很少 有人试图对其进行改动。调查人员已经表明，在 梗阻后14天内，相对拷贝数 兔膀胱线粒体基因组减少了10倍；而TCA 循环酶活性下降，细胞色素氧化酶不下降。 此外，尽管线粒体基因组拷贝数减少， 线粒体转录本保持在接近正常的水平，表明 代偿期线粒体转录。在现在 提案中，调查人员计划为以下内容定义表情变化 线粒体和核基因在代偿和失代偿中的作用 兔部分梗阻后的经期。他们还计划将 尿流动力学、膀胱肿块和膀胱肿瘤的分子表现 对自主神经激动剂、场刺激和氯化钾的收缩反应。 这些研究将增加对膀胱分子基础的理解。 梗阻后的功能障碍，可能会为 设计新的治疗工具。

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.