RELATIONSHIP BETWEEN NEUTROPHIL-MEDIATED OXIDATIVE INJURY DURING ACUTE EXPERIMENTAL PYELONEPHRITIS AND CHRONIC RENAL SCARRING
RELATIONSHIP BETWEEN NEUTROPHIL-MEDIATED OXIDATIVE INJURY DURING ACUTE EXPERIMENTAL PYELONEPHRITIS AND CHRONIC RENAL SCARRING
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DOI：
10.1128/iai.57.7.2196-2202.1989
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发表时间：
1989-07-01
影响因子：
3.1
通讯作者：
GLAUSER, MP
中科院分区：
文献类型：
--
作者：
MEYLAN, PR;MARKERT, M;GLAUSER, MP
先前对大鼠的实验表明，急性升型大肠杆菌肾盂肾炎后的肾盂肾炎瘢痕形成部分是由于肾实质中多形核白细胞（PMN）的过度浸润和激活。我们研究了急性肾盂肾炎时PMN氧化代谢在组织损伤中的作用。急性肾盂肾炎大鼠给予氨苯砜治疗（25 mg/kg，每日两次，连续3天），这是一种已知可防止PMN氧化损伤的化合物。在体外，体内容易达到的氨苯砜水平抑制髓过氧化物酶（MPO）介导的卤化物氧化为活性细胞毒性次盐的反应（如MPO介导的碘化和鲁米诺增强的化学发光）。相比之下，氨苯砜对超氧化物产生、溶酶体酶释放或活化PMN杀死细菌没有影响。在体内，氨苯砜治疗对急性肾盂肾炎在(i)细菌计数、（ii）炎症肿胀和（iii） PMN浸润方面没有显著影响。然而，与对照组相比，急性肾盂肾炎后2个月处死的经氨苯砜治疗的动物肾疤痕减少了65%。由于氨苯砜没有抗菌作用，这种保护作用与氨苯砜在急性化脓性肾盂肾炎期间通过活化的PMN细胞外释放MPO系统来防止氧化产生的组织损伤的假设是一致的。
Previous experiments with rats have suggested that pyelonephritic scarring after acute ascending Escherichia coli pyelonephritis partly results from excessive polymorphonuclear leukocyte (PMN) infiltration and activation in the kidney parenchyma. We have studied the role of PMN oxidative metabolism in generating tissue injury during acute pyelonephritis. Rats with acute pyelonephritis were treated with dapsone (25 mg/kg twice daily for 3 days), a compound known to prevent PMN oxidant damage. In vitro, levels of dapsone easily achieved in vivo inhibited myeloperoxidase (MPO)-mediated reactions involving the oxidation of halides to reactive cytotoxic hypohalites (such as MPO-mediated iodination and luminol-enhanced chemiluminescence). In contrast, dapsone had no effect on superoxide production, lysosomal enzyme release, or bacterial killing by activated PMN. In vivo, dapsone treatment had no significnat effect on acute pyelonephritis with respect to (i) bacterial counts, (ii) inflammatory swelling, and (iii) PMN infiltration. However, dapsone-treated animals sacrificed 2 months after acute pyelonephritis had a 65% reduction of renal scars when compared with controls. Since dapsone had no antibacterial effect, this protection is compatible with the hypothesis that dapsone prevented oxidant-generated tissue injury due to the extracellular release of the MPO system by activated PMN during acute suppurative pyelonephritis.