【作者】 朱深银； 周远大； 杜冠华；

【Author】 ZHU Shen-Yin*1,ZHOU Yuan-Da1,DU Guan-Hua2(1 Department of Pharmacy,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016;2 Institute of Materia Medica,Chinese Academy of Medical Science,Beijing 100050)

【机构】 重庆医科大学附属第一医院药剂科； 中国协和医科大学&中国医学科学院药物研究所；

【摘要】 目的:观察二甘醇(Diethylene glycol,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,用含0.3%、1%、3%DEG的灌流液灌流大鼠离体肾脏,监测肾脏灌流压力和尿量,测定肾小球滤过率、尿蛋白含量、肾组织内丙二醛含量(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化酶活性(glutathion peroxidase,GSH-PX)的含量或活性。体外传代培养血管内皮细胞和肾近曲小管细胞,观察二甘醇暴露后细胞形态、存活率及乳酸脱氢酶(lactate dehydrogenase,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GFR影响不明显;增加灌流肾组织MDA含量,对肾组织中SOD、GSH-PX活性无明显影响;使血管内皮细胞和肾近曲小管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,损伤作用具有明显的剂量依赖性和时间依赖性。结论:DEG能导致肾脏明显损伤,毒性作用靶细胞可能为肾脏血管内皮细胞和近曲小管细胞,损伤作用与脂质过氧化反应有关。更多还原

【Abstract】 OBJECTIVE To explore impairment effect of diethylene glycol(DEG)on kidney and target cell of toxic action in kidneys.METHODS Isolated rat kidneys were perfused with 0.3% and 1% and 3% DEG,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 contents of malonaldehyde(MDA)in kidney homogenate were assayed;vascular endothelial cell and proximal tubular epithelial cell were cultured and then exposed by DEG,cell morphology and cell viability and lactate dehydrogenase leakage were observed.RESULTS Compared with control group,perfusion pressure and urine flow rate and contents of protein in urine were significantly increased in isolated rat kidney groups perfused with DEG,yet GFR had no significant change;the contents of MDA in kidney homogenate in DEG perfusion group were also obviously increased,the activities of SOD and GSH-PX had no significant effect.Viability of vascular endothelial cell and proximal tubular epithelial cell exposed to DEG was markedly decreased,lactate dehydrogenase leakage was significantly increased,cell morphology was obviously damaged,and detriments effects had relationship of dose and time dependence.CONCLUSION DEG has an obvious damage effect on kidney,the targeted cells of intoxication are vascular endothelial cell and proximal tubular epithelial cell,the toxic role is possible related to lipid peroxidation effect.更多还原