中性粒细胞在实验性小鼠肾毒性损伤中的变化及其意义

Changes and significance of neutrophils in acute nephrotoxicity induced by high-dose cisplatin in mice

关键词:  大剂量顺铂  急性肾损伤  中性粒细胞  髓过氧化物酶  小鼠

Key words:  high-dose of cisplatin (DDP)  nephrotoxicity  polymorphonuclear neutrophil (neutrophil,PMN)  peroxidase (MPO)  mice

摘要:

［目的］探讨大剂量顺铂（Cisplatin，DDP）诱发实验性小鼠急性肾毒性损伤中中性粒细胞的变化及意义。［方法］昆明种小鼠40只，雌雄各半，依体重随机分为DDP组（12 mg/kg DDP单次腹腔内注射）和生理盐水（NS）对照组（等量NS对照）。分别取对照组小鼠10只和DDP用药后6、24、48 h小鼠各10只，内眦静脉取血，行白细胞（WBC）计数和分类计数，并检测肾脏功能。取两侧肾脏，制备10%肾皮质匀浆，比色法测定血浆和肾组织中髓过氧化物酶（Peroxidase，MPO）活性。［结果］DDP用药后48 h，小鼠血尿素氮和肌酐含量明显升高，与对照组比较差异有显著性意义（P<0.01）。小鼠外周血WBC数量DDP用药后逐渐下降，24 h 内外周血涂片中性粒细胞（polymorphonuclear neutrophil,PMN）脱颗粒明显可见；用药后48 h 血WBC计数最低，达（3.7±0.66）×109/L，与对照组（5.93±0.55）×109/L比较差异具有显著性意义（P<0.01）。小鼠外周血MPO含量DDP用药24 h内逐渐下降，用药后48 h升高，达（39.58±4.04）U/L，与对照组（19.44±5.87）U/L比较差异具有显著性意义（P<0.01）。小鼠肾皮质匀浆MPO含量DDP用药后6 h 明显升高，用药后24 h最高达（0.34±0.11）U/g，与对照组（0.13±0.03）U/g比较差异均具有显著性意义（P<0.01）；用药后48 h下降，与对照组比较差异无显著性意义（P>0.05）。 ［结论］中性粒细胞的激活，特别是肾皮质中性粒细胞MPO的释放在大剂量DDP所致小鼠肾毒性损伤早期发挥重要作用。

Abstract:

［Objective］To explore the changes and significance of neutrophils in acute nephrotoxicity induced by high-dose cisplatin in mice.［Methods］Forty Kunming mice were divided randomly into DDP group and control group according to body weight.Single dose of DDP (12 mg/kg) was intraperitoneally injected,and the same volume of natural saline (NS) was given as control.Blood samples were obtained from the orbital venous sinus of 10 mice in control group and DDP group at 6 h,24 h,48 h after DDP administration respectively.White blood cell count and differential count (DC) were performed and blood urea nitrogen (BUN) and creatinine (Cre) were measured.The levels of peroxidase (MPO) in blood and 10% renal cortical homogenate were determined by colorimetry.［Results］Plasma BUN and CRE levels were significantly increased 48 h after DDP administration (P<0.01).Degranulation response of neutrophil in blood smear could be seen within 24 h after DDP injection;Peripheral WBC counts declined gradually and dropped to (3.7±0.66)×109/L at 48 h after DDP administration,significantly lower than that (5.93±0.55)×109/L in control (P<0.01).The blood MPO level decreased slightly within 24 h,but it increased to(39.58±4.04)U/L at 48 h after DDP administration,significantly higher than that in control mice (19.44±5.87) U/L (P<0.01),while the MPO content in 10% renal cortical homogenate increased at 6 h after DDP administration,and increased to its high level (0.34±0.11) U/g at 24 h after DDP administration,significantly higher than that in control group (0.13±0.03)U/g (P<0.01),and then dropped back to normal level at 48 h after DDP administration (P>0.05).［Conclusion］Activation of neutrophils,especially the release of MPO in renal tissue in the early stage of acute renal failure plays an important role in acute nephrotoxicity induced by high-dose DDP in mice.