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[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(poly-morphonuclear 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。
[Objective] To investigate the changes and significance of neutrophils in acute nephrotoxicity induced by high-dose Cisplatin (DDP) in mice. [Method] Forty Kunming mice were randomly divided into DDP group (single intraperitoneal injection of 12 mg / kg DDP) and normal saline (NS) control group (equal NS control). 10 mice in control group and 10 mice in 6, 24 and 48 h after DDP treatment were taken respectively. The blood was collected from the internal canthal vein and the white blood cells (WBC) were counted and classified. The renal function was measured. The kidneys on both sides were taken out to prepare 10% renal cortical homogenate. The activity of myeloperoxidase (MPO) in plasma and kidney tissue was measured by colorimetry. [Result] The content of blood urea nitrogen and creatinine in mice increased significantly at 48 h after DDP treatment, which was significantly different from the control group (P <0.01). The number of WBC in peripheral blood of mice gradually decreased after DDP treatment, and the degranulation of peripheral blood mononuclear neutrophil (PMN) was visible within 24 h. The blood WBC count was the lowest at 48 h after administration (3.7 ± 0.66 ) × 109 / L, compared with the control group (5.93 ± 0.55) × 109 / L, the difference was significant (P <0.01). The level of MPO in the peripheral blood of MPO mice decreased gradually within 24 hours and increased significantly at 48 h after treatment (39.58 ± 4.04 U / L), which was significantly lower than that of the control group (19.44 ± 5.87) U / L (P <0.01). The level of MPO in the renal cortex homogenate was significantly increased at 6 h after DDP treatment and reached its peak at 24 h (0.34 ± 0.11) U / g, which was significantly lower than that of the control group (0.13 ± 0.03) U / g (P <0.01). There was no significant difference between the two groups (P> 0.05) at 48 h after treatment. [Conclusion] The activation of neutrophils, especially the release of MPO from renal cortex, plays an important role in early stage of nephrotoxicity induced by high dose DDP in mice.