Faas M M, Schuiling G A, Valkhof N, Baller J W, Bakker W W
Division of Reproductive Biology, Department of Obstetrics and Gynaecology, University of Groningen, The Netherlands.
Kidney Blood Press Res. 1998;21(6):432-7. doi: 10.1159/000025896.
In the present study the role of superoxide in the glomerular damage in the low-dose endotoxin-infused pregnant rats was investigated. On day 14 of pregnancy, 12 rats were infused for 1 h with 1.0 microgram/kg bw endotoxin via a permanent jugular vein cannula. Of these rats, 6 were treated with SOD both prior to endotoxin infusion (7,000 U/kg) and 30 min (7,000 U/kg) and 4 h (14,000 U/kg) after the start of the infusion (SOD rats). The other 6 rats received no SOD treatment (endotoxin rats). Control pregnant rats were infused for 1 h with saline (saline rats; n = 6). Urinary albumin was measured on days 15 and 19 of pregnancy. On day 21, rats were sacrificed and kidney specimens were snap-frozen. Cryostat kidney sections were stained for fibrinogen, ecto-ATP diphosphohydrolase (e-ATPase) activity, polymorphonuclear cells, monocytes and various adhesion molecules on the endothelium and the leukocytes. SOD treatment appeared to significantly prevent the increased urinary albumin excretion and the decrease of glomerular e-ATPase activity which were observed in endotoxin-treated rats. This effect of SOD treatment after endotoxin infusion was associated with a significant inhibition of glomerular monocyte influx and a significant inhibition of adhesion molecule expression (glomerular ICAM-1 and VCAM-1 and leukocyte LFA-1 and VLA-4). The present data suggest that in the endotoxin-infused pregnant rat, production of superoxide in the first few hours after the infusion plays a role in the induction of glomerular damage, leading to albuminuria and diminished e-ATPase expression during the following days.
在本研究中，我们调查了超氧化物在低剂量内毒素注入的妊娠大鼠肾小球损伤中的作用。在妊娠第14天，通过永久性颈静脉插管给12只大鼠注入1.0微克/千克体重的内毒素，持续1小时。其中6只大鼠在内毒素注入前（7000单位/千克）以及注入开始后30分钟（7000单位/千克）和4小时（14000单位/千克）接受超氧化物歧化酶（SOD）治疗（SOD大鼠）。另外6只大鼠未接受SOD治疗（内毒素大鼠）。对照妊娠大鼠注入1小时生理盐水（生理盐水大鼠；n = 6）。在妊娠第15天和第19天测量尿白蛋白。在第21天，处死大鼠并将肾脏标本速冻。低温恒温器肾脏切片进行纤维蛋白原、胞外ATP二磷酸水解酶（e-ATP酶）活性、多形核细胞、单核细胞以及内皮细胞和白细胞上各种黏附分子的染色。SOD治疗似乎能显著预防内毒素处理大鼠中观察到的尿白蛋白排泄增加和肾小球e-ATP酶活性降低。内毒素注入后SOD治疗的这种作用与肾小球单核细胞流入的显著抑制以及黏附分子表达（肾小球细胞间黏附分子-1和血管细胞黏附分子-1以及白细胞淋巴细胞功能相关抗原-1和晚期抗原-4）的显著抑制有关。目前的数据表明，在注入内毒素的妊娠大鼠中，注入后最初几小时内超氧化物的产生在肾小球损伤的诱导中起作用，导致随后几天出现蛋白尿和e-ATP酶表达减少。
