贫铀长期摄入对大鼠肾脏损伤效应的研究  

Toxic effects of depleted uranium on rat kidney after long-term ingestion

作　　者：冷言冰[1] 李蓉[1] 艾国平[1] 徐辉[1] 粟永萍[1] 程天民[1] 

机构地区：[1]第三军医大学军事预防医学院防原医学教研室,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

出　　处：《第三军医大学学报》2008年第18期1686-1689,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30500144,30670625)~~

摘　　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40只,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个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-β1、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-β1等纤维化相关因子蛋白含量均有不同程度的增加(P<0.05)。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-β1、Smad、TIMP和MMP-9均参与了其纤维化进程。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 -55 g） were fed with water and feedstuff containing 50 μLg/L or 70 μLg/kg DU respectively as ingesting group, and another 20 rats served as control. The morphological changes of kidneys were observed by electron microscopy and microscopy after 3 - , 6 - , 12 - , 18- month exposure. Fibrosis-correlated cytokines such as transforming growth factor beta 1 （TGF-β1）, 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 exposure caused pathological changes of the kidneys including glomerulus pyknosis, tubule atrophy and regional renal interstitial fibrosis. The fibrosis aggravated with longer exposure. These cytokines and collagen distribution primarily located on periphery of nephric tubule, and seldom on glomerulus. TGF- 1, Smad, TIMP-1 and MMP-9 in kidneys all increased after DU exposure. Conclusion After long-term DU exposure, the rat kidneys showed morphological and ultrastructural changes at different levels. TGF-β1, Smad, TIMP-1 and MMP-9 all take part in the process of kidney fibrosis.

关 键 词：贫铀 肾脏 纤维化 毒性 

分 类 号：R322.61[医药卫生—人体解剖和组织胚胎学] R692[医药卫生—基础医学]