顺铂致大鼠急性肾损伤肾组织细胞凋亡及NGAL的相关性研究

Relationship between Apoptosis of Renal Tubular Epithelial Cells and NGAL in the Rodent Model of Cisplatin Induced Acute Kidney Injury

目的:研究顺铂(Cisplatin,CDDP)致大鼠急性肾损伤(AKI)模型中肾组织细胞凋亡及肾组织中性粒细胞明胶酶相关脂质运载蛋白(NGAL)变化及相关性。方法:将36只健康雄性Wistar大鼠随机分为盐水对照组(CN组)与顺铂模型组(CP组),CP组为腹腔单次注射顺铂10 mg/kg,CN组腹腔注射同顺铂组等容量生理盐水,观察应用顺铂后12、24、48、96、144 h各组大鼠血清肌酐(Scr),肾组织细胞凋亡及NGAL变化。结果:与CN组相比,CP组48 Scr开始升高,144 h达峰值;CP组12 h肾组织凋亡细胞开始增多,48 h增加最明显;CP组12 h NGAL在肾小管上皮细胞中表达增强(P<0.05),48 h表达最明显。肾组织细胞凋亡同NGAL表达显著相关(r=0.925,P<0.01)。结论:细胞凋亡可能是CDDP致大鼠AKI早期致病机制之一,NGAL不仅是早期肾损伤的标记物,还可能参与AKI发病机制。

Objective： To observe the relationship between apoptosis of renal tubular epithelial ceils and NGAL in the rodent model of Cisplatin induced acute kidney injury.Method： A total of 36 male wistar rats were randomly assigned to different groups.The rats of CP group were injected once intraperitoneal with Cisplatin at 10 mg/kg, the rats of CN group were injected intraperitoneal with same volume of normal saline vehicle.Rats were euthanized at 12, 24, 48, 96 and 144 hours （n=6 in the CP group at each time point ） .The blood and renal tissue specimens were analyzed at each time point.Result： Significant elevations of ereatnine in serum were noted by 48 hours in the CP group versus CN group, peak levels were seen on 144 hours （ P〈0.05 ） .A significant increased expression of NGAL in renal tissue sections was noted by 12 hours in the CP group versus CN group, the most obvious expression of NGAL was seen on 48 hours （ P〈0.05 ） .In addition, renal epithelial cells apoptosis was noted by 12 hours in the CP group versus CN group, peak level was seen on 48 hours （ P〈0.05 ） .Apoptosis of renal tubular epithelial cells and NGAL expression was significantly correlated （r=0.925, P〈0.01 ） .Conclusion： Apoptosis may be involved in the early pathogenesis of AKI induced by CDDP in rodent modals, NGAL is not only a biomarker of early renal injury, but also may be involved in the pathogenesis of AKI.