Paller M S
Department of Medicine, University of Minnesota, Minneapolis 55455.
J Lab Clin Med. 1989 Mar;113(3):379-86.
Oxygen free radicals have been implicated in postischemic renal injury. However, the source of these oxygen free radicals has not been well defined. One potential source is activated neutrophils. Neutrophil depletion was produced in rats by using two different techniques, and the effect on ischemic injury was examined. Rabbit anti-rat neutrophil serum was prepared by immunizing a rabbit with a Percoll gradient centrifugation-purified (approximately 90%) suspension of rat neutrophils. Rats received antineutrophil serum in one of four protocols and were subsequently subjected to 40 minutes of renal artery occlusion. Control animals received nonimmune rabbit serum. The serum creatinine levels 24 hours after ischemia were not different between control and immune serum-treated rats in any of the protocols despite significant reductions in absolute neutrophil count. In a separate study, nitrogen mustard was administered 40 hours before ischemia. Nitrogen mustard-treated rats developed moderate neutropenia and 24 hours after ischemia had lower serum creatinine levels and higher inulin clearance. However, nitrogen mustard-treated rats lost 31.5 +/- 5 gm body weight in the 2 days after nitrogen mustard administration, whereas control animals gained 5.9 +/- 5.9 gm during the same interval. Furthermore, among nitrogen mustard-treated rats there was no correlation between neutrophil count and postischemic renal function. It is thus possible that the beneficial effects of nitrogen mustard were caused by a mechanism other than neutrophil depletion. In summary, in four protocols that used antineutrophil serum, neutropenia did not protect against ischemic injury. Nitrogen mustard provided protection, but probably by a neutrophil-independent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
氧自由基与缺血后肾损伤有关。然而，这些氧自由基的来源尚未明确界定。一个潜在来源是活化的中性粒细胞。通过两种不同技术使大鼠中性粒细胞减少，并检测其对缺血性损伤的影响。用经Percoll梯度离心纯化（约90%）的大鼠中性粒细胞悬液免疫兔子制备兔抗大鼠中性粒细胞血清。大鼠按四种方案之一接受抗中性粒细胞血清，随后进行40分钟肾动脉闭塞。对照动物接受非免疫兔血清。尽管绝对中性粒细胞计数显著降低，但在任何方案中，缺血24小时后对照大鼠和免疫血清处理大鼠的血清肌酐水平并无差异。在另一项研究中，在缺血前40小时给予氮芥。氮芥处理的大鼠出现中度中性粒细胞减少，缺血24小时后血清肌酐水平较低，菊粉清除率较高。然而，氮芥处理的大鼠在给予氮芥后2天体重减轻31.5±5克，而对照动物在同一时期体重增加5.9±5.9克。此外，在氮芥处理的大鼠中，中性粒细胞计数与缺血后肾功能之间无相关性。因此，氮芥的有益作用可能是由中性粒细胞减少以外的机制引起的。总之，在使用抗中性粒细胞血清的四种方案中，中性粒细胞减少并不能预防缺血性损伤。氮芥提供了保护作用，但可能是通过一种不依赖中性粒细胞的机制。（摘要截短至250字）
