二甘醇诱发肾脏损伤的作用研究.doc

二甘醇肾脏损伤 朱深银*1周远大杜冠华重庆医科大学重庆 400016中国协和医科大学医学科学院药物研究所北京 100050（Diethylene glycol，DEG）离体肾脏灌流技术0.3%、1%、3% DEG大鼠离体灌流压力尿量肾小球滤过率尿蛋白含量、肾组织丙二醛（malondialdehyde，MDA）、超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽过氧化酶（glutathion peroxidase，GSH-PX）的含量或活性血管内皮细胞肾近曲小管细胞观察二甘醇细胞存活率及（lactate dehydrogenaseLDH）DEG增加离体灌流大鼠肾脏的灌流压力尿量和尿蛋白含量对GFR影响明显；增加灌流肾MDA含量，对肾SOD、GSH-PX活性无明显影响血管内皮细胞肾近曲小管细胞细胞活力明显下降，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 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离体肾脏灌流血管内皮细胞近曲肾小管细胞 Impairment Effect of Diethylene Glycol on Kidney 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) 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