贫铀长期摄入对大鼠肾脏损伤效应的研究.docVIP

PAGE PAGE 2 贫铀长期摄入对大鼠肾脏损伤效应的研究 冷言冰*, 李蓉, 艾国平, 徐 辉, 粟永萍, 程天民基金项目 基金项目:全军“十五”指令性课题(01L061), 军队“十一五”专项项目（06Z031） Supported by the Mandatory Scientific Research Project of the “Tenth Five-Year Plan” of PLA (01L061) and the Foundation of the “Eleventh Five-Year Plan” for Medical Science Development of PLA (06Z031) 作者简介:冷言冰(1973-),男，山东烟台人，汉族，博士，讲师，主要从环境毒理学方面的研究，发表论文6篇。电话： （028手机作者现单位：成都医学院公共卫生学教研室，610083，email：lengyanbing@ (第三军医大学军事预防医学院全军复合伤研究所，创伤烧伤与复合伤国家重点实验室，重庆400038) 提要：目的 研究贫铀摄入后不同时相点对大鼠肾脏的损伤效应。方法 雄性Wistar大鼠，共40只，35-55g，其中20只以含有50μg/L和70μg /kg的贫铀饮水及饲料喂食大鼠作为摄入组。观察大鼠接触贫铀后3、6、12、18月大鼠肾脏超微结构和病理形态学改变,肾功能检测和胶原染色，并采用免疫荧光和蛋白印记杂交检测肾脏不同时间段纤维化相关因子TGF-?1、Smad、TIMP和MMP-9表达。结果 大鼠摄入贫铀后不同时间段大鼠肾脏出现不同程度的病理改变，表现为肾小球固缩、后继肾小管萎缩和局部肾间质纤维组织增生以及炎性细胞浸润。纤维化程度随接触时间延长而加重。胶原染色显示胶原分布主要位于肾小管周围，且具有区域性。Western blot分析显示贫铀接触后大鼠肾脏中TGF-?1等纤维化相关因子蛋白含量均有不同程度的增加。结论 贫铀长时间暴露后大鼠肾脏可出现病理学及超微结构的改变，TGF-?1、 Smad、TIMP和MMP-9均参与了其纤维化进程。 关键词：贫铀、肾脏、纤维化、毒性 Toxic effects of depleted uranium on rat kidney after long-term ingestion LENG Yan-bing, LI Rong, AI Guo-ping, XU Hui, SU Yong-ping, CHENG Tian-min (State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Combined Injury, College of Preventive Medicine, Third Military Medical Abstract: Objective To study the toxic effects on rat kidney after long-term depleted uranium (DU) exposure. Methods Twenty rats of 40 Wistar male rats (35-55g) were fed with water and feedstuff containing 50 μg/L or 70 μg /kg DU respectively as ingesting group, and another 20 rats served as control. The morphological changes of kidneys were observed by electronmicroscopy and microscopy after 3-, 6-, 12-, 18-month exposure.　Fibrosis-correlated cytokines such as transforming growth factor beta 1 (TGF-?1), Smad, tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinases-9 (MMP-9) were analyzed by immunofluorescence and Western blotting. Kidney function and collagen staining were also detected. Results At different time points, DU exposu