二甘醇对大鼠肾脏的损伤作用

Impairment effect of diethylene glycol on kidney

目的观察二甘醇(DEG)致肾脏损伤的作用特点,并探讨其毒性作用靶细胞。方法采用离体肾脏灌流技术,分别用含0.3%,1.0%和3.0%DEG的灌流液灌流大鼠离体肾脏90min,监测肾脏灌流压力和尿量,测定肾小球滤过率、尿蛋白含量、肾组织内丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化酶(GSH-Px)的活性。体外传代培养人脐静脉内皮细胞株(EA.hy926)和人肾近曲小管上皮细胞株(HK-2),观察DEG0.1～1.0mmol.L-1暴露2～24h后,细胞形态、存活率及乳酸脱氢酶(LDH)漏出变化。结果DEG增加离体灌流大鼠肾脏的灌流压力、尿量和尿蛋白含量,但对肾小球滤过率影响不明显;使灌流肾组织中SOD和GSH-Px活性降低,MDA含量增加。DEG使EA.hy926细胞和HK-2细胞的细胞活力明显下降,LDH漏出明显增加,细胞形态明显改变。损伤具有明显的浓度和时间依赖性。结论DEG能导致肾脏明显损伤,毒性作用靶细胞可能为肾脏的血管内皮细胞和近曲小管上皮细胞,损伤作用与脂质过氧化反应有关。

AIM To explore impairment effect of diethylene glycol（DEG） on kidneys and target cell of toxic action in kidneys.METHODSIsolated rat kidneys were perfused with 0.3%,1% and 3% DEG for 90 min.Perfusion pressure,glomerular filtration rate（GFR） and urine flow rate were monitored.The contents of protein in urine,the activities of superoxide dismutase（SOD） and glutathione peroxidase（GSH-Px） and the content of malonaldehyde（MDA） in kidney homogenate were assayed.Human umbilical vein endothelial（EA.hy926） cells and proximal tubular epithelial（HK-2） cells were cultured and then exposed to DEG 0.1-1.0 mmol·L^-1 for 2-24 h,cell morphology,cell viability and lactate dehydrogenase（LDH） leakage were observed.RESULTSCompared with control group,perfusion pressure,urine flow rate and content of protein in urine significantly increased in isolated rat kidney perfused with DEG,but GFR had no significant change;and the activities of SOD and GSH-Px significantly lowered and the content of MDA obviously increased in kidney homogenate in DEG perfusion groups.Viabilities of EA.hy926 cells and HK-2 cells exposed to DEG markedly decreased,LDH leakage significantly increased and cell morphology was obviously damaged.The detriment was concentration-and time-dependence.CONCLUSIONDEG has damage effects on rat kidneys.The targeted cells of intoxication may be vascular endothelial cells and proximal tubular epithelial cells,and the toxic mechanism possibly relates to the decrease in antioxidation enzyme activities and augmentation of lipid peroxidation.