Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Urology. 2011 Apr;77(4):1008.e1-8. doi: 10.1016/j.urology.2010.11.018. Epub 2011 Jan 22.
To investigate the relationship between nitric oxide synthase (NOS) and oxidative stress and pathologic remodeling in the partial obstructed bladder of a rat model.
We surgically established partial bladder outlet obstruction (PBOO) in 2 groups of rats and allowed it to persist for 3-6 weeks. Normal and sham-operated rats served as the controls. Each group contained 6 rats for a total of 24 rats. Cystometry was used to evaluate the bladder function. The bladders were removed, and histopathologic measurements were performed to evaluate bladder hypertrophy and fibrosis and NOS immunolocalization. Biochemical measurements were used to evaluated NOS mRNA and activity and the oxidative stress level.
The obstructed rats experienced significant increases in bladder weight, muscle hypertrophy, and deposits of collagen fibers compared with the normal and sham-operated groups. PBOO debilitated bladder contractibility, increased the residual urine volume and voiding interval, decreased the voiding volume, and caused poor bladder emptying, with an increased residual urine volume and decompensated bladder in the PBOO rats at 6 weeks. The elevation in malondialdehyde and reduction in superoxide dismutase activity in the PBOO rats suggested that oxidative stress injury occurred in the obstructed bladder. Lower inducible NOS and endothelial NOS (eNOS) mRNA expression was demonstrated through quantitative polymerase chain reaction. In particular, eNOS was significantly downregulated in the PBOO rats compared with the normal and sham-operated rats. The normal and PBOO bladder tissues did not express detectable levels of neuronal NOS mRNA or exhibit neuronal NOS immunoreactivity. The total NOS activity had decreased progressively in the PBOO groups in conjunction with the significantly decreased eNOS activity compared with that in the normal and sham-operated groups.
These findings suggest that decreases in NOS activity and expression (mainly of eNOS) concomitant with increases in reactive oxygen species generation represent the underlying pathogenic mechanism of obstructed bladder remodeling and dysfunction.
研究一氧化氮合酶（NOS）与氧化应激和大鼠部分梗阻性膀胱病理重塑之间的关系。
我们在两组大鼠中建立了部分膀胱出口梗阻（PBOO）手术，并使其持续 3-6 周。正常和假手术大鼠作为对照。每组 6 只大鼠，共 24 只大鼠。膀胱测压用于评估膀胱功能。取出膀胱，进行组织病理学测量以评估膀胱肥大和纤维化以及 NOS 免疫定位。生化测量用于评估 NOS mRNA 和活性以及氧化应激水平。
与正常和假手术组相比，梗阻大鼠的膀胱重量、肌肉肥大和胶原纤维沉积明显增加。PBOO 削弱了膀胱的收缩性，增加了残余尿量和排尿间隔，减少了排尿量，导致膀胱排空不良，残余尿量增加，PBOO 大鼠在 6 周时膀胱代偿失调。PBOO 大鼠丙二醛升高，超氧化物歧化酶活性降低，提示梗阻膀胱发生氧化应激损伤。通过定量聚合酶链反应显示诱导型 NOS 和内皮型 NOS（eNOS）mRNA 表达降低。特别是 eNOS 在 PBOO 大鼠中的表达明显低于正常和假手术大鼠。正常和 PBOO 膀胱组织未检测到神经元型 NOS mRNA 或表现出神经元型 NOS 免疫反应性。与正常和假手术组相比，PBOO 组的总 NOS 活性逐渐降低，同时 eNOS 活性显著降低。
这些发现表明，NOS 活性和表达（主要是 eNOS）的降低伴随着活性氧生成的增加，是梗阻性膀胱重塑和功能障碍的潜在发病机制。
