汞中毒致大鼠肾病综合征模型的建立  

The model of nephrotic syndrome induced by mercury intoxication in rats

作　　者：陈子安[1] 隋昕[2] 聂志勇[2] 李万华[2] 邱泽武[1] 王永安[2] 

机构地区：[1]军事医学科学院附属医院,北京100071 [2]抗毒药物与毒物学国家重点实验室(军事医学科学院),北京100850

出　　处：《中国急救医学》2015年第5期449-454,I0002,共7页Chinese Journal of Critical Care Medicine

基　　金：基金项目：全军医学科技“十二五’’重大项目（AWS11C004）及重点项目（BWS12J042）;国家新药创制重大专项（2011ZXJ09102-05C,2011ZXJ-09305）

摘　　要：目的：建立汞中毒致大鼠肾病综合征模型，为临床相关治疗手段的验证和筛选提供稳定、科学的验证平台。方法 Brown－Norway rats（ BN大鼠）雄性24只，随机分为三个不同剂量的模型组（0．5、1．0及2．0 mg／kg氯化汞溶液）及一个对照组（生理盐水组），隔天一次腹部皮下注射，并在第7、14、21、28、35天分别监测尿蛋白、血生化、汞含量、病理等指标，从而确定出1．0 mg／kg为建立模型的合适剂量。另取24只大鼠，随机选取18只为模型组，按上述方法注射1．0 mg／kg氯化汞溶液，另外6只为对照组，并于第15、22、36天将其分别处死，检测肾中汞的蓄积情况。结果染毒后第14天，各模型组与对照组比较均出现了不同程度的尿蛋白升高、血浆白蛋白降低、高脂血症及水肿；病理切片中各剂量组均出现不同程度的肾损伤；血、尿中汞含量有明显的剂量－效应关系。其中1．0 mg／kg剂量组血生化、尿蛋白定量各项指标与生理盐水组比较差异最为明显且水平较稳定，病理检查发现有典型的肾病综合征病变，肾中汞含量检测显示，1．0 mg／kg剂量组出现了汞在肾脏的蓄积。结论 BN大鼠在隔天给药、腹部皮下注射氯化汞1．0 mg／kg、7针停药（2周）的情况下可以建立较理想的汞中毒致大鼠肾病综合征模型。Objective The present study aims to establish a model of nephrotic syndrome induced by mercury intoxication, in order to provide stable and scientific platform for clinical relevant treatment.Methods Twenty-four male BN rats were randomly divided into four groups, including three model groups（ n=18） and a control group（ n=6） .The rats in the three model groups were given respectively mercuric chloride solution by subcutaneous injection of 0.5, 1.0 and 2.0 mg/kg and the control group was given a subcutaneous injection of saline, all the rats were given once every other day. By monitored the urine protein, blood biochemical indicators, mercury pontent, pathological section after injected for 7, 14, 21, 28, 35 days, we identified 1.0 mg/kg was the right dose to establish the model. Another 24 rats were randomly divided into 3 groups, according to the above method the including 18 rats were all injected in 1 mg/kg mercury chloride, the other 6 rats were for the control group.On day 15, 22 and 36 the rats were sacrificed and rat kidneys were sampled to monitor the mercury content in order to observe the accumulation of mercury in the kidney.Results Fourteen days after mercury injection, high proteinuria, low albumin, hyperlipidemia and edema occurred in three model groups, and obvious pathological change of kidney damage was also shown in three model groups.Mercury content in blood＆amp;nbsp;and urine showed there was obvious dose -effect relationship.Compared with the control group, the related symptoms were the most prominent and stable with 1mg/kg dose group.There was a typical pathological types with nephrotic syndrome under light microscope with 1 mg/kg dose group and mercury accumulation in kidney tissues after stopped the injection.Conclusion It may be a reliable model of nephrotic syndrome induced by mercury intoxication in BN rats, which are injected subcutaneously with 1 mg/kg mercuric chloride solution once every other day for two weeks.

关 键 词：BN大鼠 汞中毒 肾病综合征 模型建立 

分 类 号：R692[医药卫生—泌尿科学]