Ruiz-Torres P, Lucio J, González-Rubio M, Rodríguez-Puyol M, Rodríguez-Puyol D
Department of Physiology, Alcalá de Henares University, Spain.
Free Radic Biol Med. 1997;22(1-2):49-56. doi: 10.1016/s0891-5849(96)00239-0.
The mechanisms responsible for age-related glomerular sclerosis (GS) have not been clearly identified. The present experiments were aimed at assessing the importance of the oxidant/antioxidant balance in the early stages of this process. For this purpose, the renal function (biochemical and clearance studies), some characteristics of isolated glomeruli, and reactive oxygen production (superoxide anion, hydrogen peroxide) as well as the antioxidant ability (superoxide dismutase, catalase, glutathione peroxidase) of glomeruli and cultured mesangial cells were studied in 3- and 18-month-old Fischer 344 rats (YOUNG and OLD rats, respectively). OLD animals show a normal renal function, increased urine protein excretion, and augmented protein glomerular content, an indirect index of GS. Isolated glomeruli from these rats produced increased amounts of superoxide anion and hydrogen peroxide, and catalase activity was increased. The glomerular thiobarbituric acid-reactive substances (TBARS) content was higher in OLD than in YOUNG animals. Similar results were obtained in cultured mesangial cells. In summary, the present results demonstrate, at an early stage of rat GS development, an association between the functional and structural changes of this process and an increased TBARS content (likely indicative of lipid oxidative damage) at the glomerular structures as well as in cultured mesangial cells. More extensive studies are needed to confirm the nature of this association.
与年龄相关的肾小球硬化（GS）的发病机制尚未完全明确。本实验旨在评估氧化还原平衡在此过程早期阶段的重要性。为此，我们研究了3月龄和18月龄的Fischer 344大鼠（分别为年轻大鼠和老年大鼠）的肾功能（生化和清除率研究）、分离肾小球的一些特性、活性氧生成（超氧阴离子、过氧化氢）以及肾小球和培养的系膜细胞的抗氧化能力（超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶）。老年动物肾功能正常，但尿蛋白排泄增加，肾小球蛋白含量升高，这是GS的一个间接指标。这些大鼠分离出的肾小球产生的超氧阴离子和过氧化氢量增加，过氧化氢酶活性增强。老年动物肾小球中硫代巴比妥酸反应性物质（TBARS）含量高于年轻动物。在培养的系膜细胞中也得到了类似结果。总之，本研究结果表明，在大鼠GS发生的早期阶段，该过程的功能和结构变化与肾小球结构及培养的系膜细胞中TBARS含量增加（可能提示脂质氧化损伤）之间存在关联。需要更广泛的研究来证实这种关联的性质。
