【摘要】  目的 研究贫铀植入后不同时相点对大鼠肾脏的损伤效应。方法 采用初成年健康雄性Wistar大鼠分别植入贫铀片，观察大鼠接触贫铀后3、6、12、18月其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-β 1与Smad表达。结果 植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。TGF-β 1与Smad是肾脏组织纤维化进程中重要的细胞因子。Western Blot分析显示贫铀接触后大鼠肾脏中TGF-β 1与Smad均有不同程度的增加。结论 贫铀长时间植入后大鼠肾脏可出现病理学及超微结构的改变，TGF-β 1与Smad参予了其纤维化进程。

【关键词】  贫铀 肾脏 纤维化 毒性

    Abstract：Objective To study the toxic effects on rat kidney after long term depleted uranium(DU)exposure.Methods Twenty adult male rats were implanted DU plates as implanted group.The morphology changes of kidneys were observed by electronmicroscopy and microscopy after 3,6,12,18 months exposure.Fibrosis-correlated cytokines such as TGF-β1 and Smad were analyzed by immunofluorescence and Western Blotting.Kidney function and collagen staining were also fulfilled.Results At different time-point,the morphological structure observation showed that DU exposure can cause the kidney fibrosis among which glomerulus pyknosis,tubule atrophy and regional renal interstitial fibrosis.The fibrosis became aggravated with longer exposure.The analysis and collagen staining showed that these cytokines and collagen distribution primarily located on periphery of nephric tubule,and seldom on glomerulus if any.TGF-β1 and Smad are important factors for tissue fibrosis. Western Blot analysis showed that Transforming Growth Factor beta 1(TGF-β1) and Smad in kidney all increased after DU exposure.Conclusion After long term DU exposure,the rats kidneys showed morphology and ultrastructure changes at different levels.TGF-β1 and Smad both took part in the process of fibrosis.

    Key words:depleted uranium；kidney；fibrosis；toxicity

    贫铀(Depleted Uranium，DU)是铀原料经浓缩提取235U以后所产生的副产品，因其235U含量低于天然铀故而得名。目前DU合金被广泛应用于各类民用和军事项目。贫铀既具

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