Glomerular oxidative and antioxidative systems in experimental mesangioproliferative glomerulonephritis
Glomerular oxidative and antioxidative systems in experimental mesangioproliferative glomerulonephritis
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DOI：
10.1097/01.asn.0000034908.43113.5d
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发表时间：
2002-12-01
影响因子：
13.6
通讯作者：
Gwinner, W
中科院分区：
文献类型：
--
作者：
Gaertner, SA;Janssen, U;Gwinner, W
肾小球系膜细胞增殖增加是人类许多肾小球病的标志。尽管活性氧（ROS）在实验性系膜增生性肾小球肾炎（GN）的发病中的作用已经得到了很好的证实，但对导致肾小球中ROS浓度升高的机制却知之甚少。因此，本研究检查肾小球ROS和活性的氧化和抗氧化酶在系膜增生性抗Thy 1.1 GN的早期过程。在雄性Wistar大鼠中诱导抗Thy 1.1 GN，并在疾病诱导后2、24和120 h分离肾小球，以检查ROS水平以及与非肾炎对照相比的氧化和抗氧化酶表达。在所有时间点，观察到肾小球ROS水平增加，特别是过氧化氢和超氧阴离子。在GN过程中，NADH依赖性和NADPH依赖性氧化酶的活性也增加，而另一个潜在的ROS来源黄嘌呤氧化酶的活性没有增加。尽管肾小球氧化应激，抗氧化酶活性没有代偿性增加。相反，过氧化氢酶，超氧化物歧化酶，谷胱甘肽过氧化物酶活性甚至下降，在病程中。在肾小管间质样品中，在疾病过程中没有观察到氧化活性的增加，从而证实检测到的ROS是肾小球来源的。我们的数据首次记录了系膜增生性肾小球肾炎中促氧化和抗氧化酶的明显失调，导致肾小球ROS水平的净增加。对这些途径的详细了解可能会导致人类GN的新治疗方法。
Increased mesangial cell proliferation is a hallmark of many glomerulopathies in humans. Whereas the pathogenic role of reactive oxygen species (ROS) in the development of experimental mesangiciproliferative glomerulonephritis (GN) is well established, very little is known about the mechanisms leading to increased ROS concentrations in the glomerulus. This study therefore examined glomerular ROS and the activities of oxidative and antioxidative enzymes during the early course of mesangioproliferative anti-Thy 1.1 GN. Anti-Thy 1.1 GN was induced in male Wistar rats, and glomeruli were isolated 2, 24, and 120 h after disease induction to examine ROS levels as well as oxidative and antioxidative enzyme expression in comparison to non-nephritic controls. At all time points, increased glomerular ROS levels, particularly of hydrogen peroxide and superoxide anions, were observed. Activities of NADH-dependent and NADPH-dependent oxidative enzymes were also increased during the course of GN, whereas no increased activity of xanthine oxidase, another potential source of ROS, was detectable. Despite glomerular oxidative stress, no compensatory increase of antioxidative enzyme activities occurred. On the contrary, catalase, superoxide dismutase, and glutathione peroxidase activities even decreased during the course of disease. In tubulointerstitial samples, no increase in oxidative activity was observed in the course of disease, thus confirming that detected ROS were of glomerular origin. Our data document for the first time a pronounced dysregulation of pro-oxidative and antioxidative enzymes in mesangioproliferative GN, leading to a net increase in glomerular ROS levels. Detailed knowledge of such pathways may lead to new therapeutic approaches for GN in humans.