ROLE OF IRON IN POSTISCHEMIC RENAL INJURY IN THE RAT
ROLE OF IRON IN POSTISCHEMIC RENAL INJURY IN THE RAT
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DOI：
10.1038/ki.1988.205
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发表时间：
1988-10-01
影响因子：
19.6
通讯作者：
WATERFIELD, R
中科院分区：
文献类型：
--
作者：
PALLER, MS;HEDLUND, BE;WATERFIELD, R
为了确定铁是否参与自由基介导的缺血后肾损伤和脂质过氧化，我们研究了肾缺血后去除内源性铁或提供外源性铁的影响，以及肾缺血和再灌注对肾静脉和尿“游离”铁的影响。大鼠经历60分钟的肾缺血，并在再灌注24小时（菊粉清除率）或15分钟（肾丙二醛含量）后进行研究。在再灌注的前60分钟内输注铁螯合剂去铁胺（200 mg/kg/hr）导致肾功能的显著改善（菊粉清除率：879 ± 0.01）。154对314 +-。74 μ l/min; P < 0.025）和脂质过氧化作用的降低（肾丙二醛：0.449 ± 0.74 μ l/min; P <0.025）。0.06对0.698 ±。0.08 mmol/mg蛋白; P < 0.05）。输注50 mg/kg/hr的去铁胺也保护缺血后的肾功能（菊粉清除率：624 ± 0.9%）。116对285 +-。90 μ l/min; P < 0.05），并导致较少的组织学损伤。铁饱和的去铁胺没有保护作用。相反，在再灌注期间输注铁复合物EDTA-FeCl 3加剧了缺血后肾功能障碍和脂质过氧化。肾缺血后，动脉或肾静脉血浆中的“游离”铁没有检测到增加。然而，尿中的“游离”铁在再灌注后增加了10- 20倍。铁螯合剂，经过过滤，并获得了这种游离铁在尿液中（游离去铁胺或菊糖共轭去铁胺）提供保护，而螯合剂局限于血管空间（葡聚糖共轭去铁胺）没有。我们建议，在缺血和再灌注铁从存储池中释放，并可用于催化羟基自由基的形成和脂质过氧化。在再灌注期间给予铁螯合剂去铁胺限制缺血后肾功能不全和自由基介导的脂质过氧化。这些效应似乎发生在泌尿空间或沿着邻近泌尿空间的刷状缘膜。
To determine whether iron participates in free radical-mediated postischemic renal injury and lipid peroxidation, we examined the effects of removal of endogenous iron or provision of exogenous iron following renal ischemia, as well as the effects of renal ischemia and reperfusion on renal venous and urinary "free" iron. Rats underwent 60 minutes of renal ischemia and were studied after either 24 hours (inulin clearance) or 15 minutes (renal malondialdehyde content) of reperfusion. Infusion of the iron chelator deferoxamine (200 mg/kg/hr) during the first 60 minutes of reperfusion resulted in a marked improvement in renal function (inulin clearance: 879 .+-. 154 vs. 314 .+-. 74 .mu.l/min; P < 0.025) and a reduction in lipid peroxidation (renal malondialdehyde: 0.449 .+-. 0.06 vs. 0.698 .+-. 0.08 mmol/mg prot; P < 0.05) compared to control animals. Infusion of 50 mg/kg/hr deferoxamine also protected renal function after ischemia (inulin clearance: 624 .+-. 116 vs. 285 .+-. 90 .mu.l/min; P < 0.05) and resulted in less histologic injury. Iron-saturated deferoxamine had no protective effect. Conversely, infusion of the iron complex EDTA-FeCl3 during reperfusion exacerbated postischemic renal dysfunction and lipid peroxidation. Following renal ischemia there was no detectable increase in "free" iron in arterial or renal venous plasma. However, urinary "free" iron increased 10- to 20-fold following reperfusion. Iron chelators which underwent filtration and gained access to this free iron in the urine (free deferoxamine or inulin-conugated deferoxamine) provided protection, whereas a chelator confined to the vascular space (dextran-conjugated deferoxamine) did not. We propose that during ischemia and reperfusion iron is released from storage pools and is available to catalyze hydroxyl radical formation and lipid peroxidation. Administration of the iron chelator deferoxamine during reperfusion limits postischemic renal dysfunction and free radical-mediated lipid peroxidation. These effects appear to take place in the urinary space or along the brush border membrane adjacent to the urinary space.