Regulation of Free Radical Production in Experimental Renal Disease

为探讨自由基(ROS)在实验性肾小球损伤发病机制中的重要作用，采用肾小球化学发光法(GCL)对实验性肾病大鼠进行了肾小球化学发光分析，并用自由基清除剂进行治疗。在肾小球肾炎中，用组织化学和GCL法研究细胞动力学。在抗肾小球基底膜肾小球肾炎中，肾小球内多形核白细胞(PMN)或巨噬细胞的活化导致肾小球GCL增多，反映ROS的生成。过氧化氢酶或超氧化物歧化酶对中性粒细胞浸润期大鼠的蛋白尿有保护作用，并可降低内生肌酐清除率。在抗Thy-1肾炎中，ROS的产生与巨噬细胞的浸润一致。而氨基核苷(PAN)或阿霉素肾病大鼠肾小球GCL也明显升高，提示肾小球内ROS的产生。自由基清除剂潘生丁和地拉西普对PAN肾病有保护作用，可抑制PAN中GCL的升高，提示抗氧化剂在治疗肾小球病变中有一定作用。这些结果还阐明，这些清除剂应与浸润性细胞和/或肾小球驻留细胞产生ROS的阶段同时使用。

To investigate substantial role of free radical (reactive oxygen species (ROS)) in the pathogenesis of experimental glomerula injury, glomerular chemiluminescence (GCL) assay were performed in rat experimental renal diseases together with treatment with radical scavengers. In glomerulonephritis, cell kinetics using histochemistry were studied along with GCL assay. In anti-glomerular basement membrane glomerulonephritis, GCL increased reflecting ROS generation due to activated polymorphonuclear leukocyte (PMN) or macrophage infiltrated in glomerulus. Protective effect on proteinuria and decrease of creatinine clearance were noted in rats with catalase or SOD treatment during the phase of PMN infiltration. In anti-Thy-1 nephritis, ROS production was consistent with macrophage infiltration. On the other hand glomeruli from puromycin aminonucleoside (PAN) or adriamycin nephrosis rat, showed also increase of GCL suggesting ROS production from glomerular resident cells. Suppression of increased GCL in PAN by radical scavenger, dipyridamole and dilazep, which reportedly have protective effect on PAN nephrosis, indicated that antioxidant can play a role in the therapy of glomerular lesion. These results also elucidated that these scavengers should be administered concomitantly with ROS generating phase from the infiltrating cells and/or glomerular resident cells.