Szabo Attila J, Wagner Laszlo, Erdely Aaron, Lau Kim, Baylis Chris
Department of Physiology, West Virginia University, Morgantown, West Virginia 26506, USA.
Kidney Int. 2003 Nov;64(5):1765-71. doi: 10.1046/j.1523-1755.2003.00260.x.
Animal studies suggest that nitric oxide deficiency occurs in the remnant after 5/6 removal of renal mass. The present studies investigated the time course in relation to progression of renal disease, as well as the impact on individual renal nitric oxide synthase (NOS) isoforms.
Rats were studied from 2 to 11 weeks after 5/6 ablation/infarction (A/I) of renal mass, with acceleration of progression by high protein and salt intake, in some groups. Measurements were made before sacrifice of 24-hour protein and creatinine excretion, blood was taken for creatinine and blood urea nitrogen (BUN) determination and the kidneys were investigated histologically for structural damage, abundance of endothelial NOS (eNOS) and neuronal NOS (nNOS), and in some groups for in vitro NOS activity.
A time-dependent fall in glomerular filtration rate (GFR) and rise in proteinuria and glomerular sclerosis developed after 5/6 A/I. The nNOS abundance in cortex and medulla was decreased relative to shams, in all but the mildest injury and there was a strong, steep correlation between level of glomerular sclerosis and the degree of reduction in renal nNOS. Where measured, cortical NOS activity correlated with the nNOS abundance. In contrast, the eNOS abundance was either increased or unchanged in rats post A/I.
Renal nNOS abundance was reduced in the 5/6 A/I model of renal disease when plasma creatinine> approximately 1 mg/dL and when> approximately 20% of remaining glomeruli were sclerosed.
动物研究表明，在切除5/6肾组织后的残余肾中会出现一氧化氮缺乏。本研究调查了与肾脏疾病进展相关的时间进程，以及对各个肾脏一氧化氮合酶（NOS）亚型的影响。
对大鼠在5/6肾切除/梗死（A/I）后2至11周进行研究，部分组通过高蛋白和高盐饮食加速疾病进展。在处死前测量24小时蛋白质和肌酐排泄量，采集血液测定肌酐和血尿素氮（BUN），并对肾脏进行组织学检查，以评估结构损伤、内皮型NOS（eNOS）和神经元型NOS（nNOS）的丰度，部分组还检测体外NOS活性。
5/6 A/I后，肾小球滤过率（GFR）呈时间依赖性下降，蛋白尿和肾小球硬化增加。除最轻微损伤外，皮质和髓质中的nNOS丰度相对于假手术组均降低，肾小球硬化程度与肾脏nNOS降低程度之间存在强烈、陡峭的相关性。在检测的部位，皮质NOS活性与nNOS丰度相关。相比之下，A/I后大鼠的eNOS丰度要么增加，要么不变。
在血浆肌酐>约1 mg/dL且>约20%的剩余肾小球硬化时，5/6 A/I肾病模型中肾脏nNOS丰度降低。
