汞致肾病综合征大鼠肾损伤及细胞凋亡  

Mechanism of renal injury and apoptosis in rats with nephrotic syndrome induced by mercury

作　　者：孙琳 李侠[2] 尚磊[2] 郑熠娇 Sun Lin;Li Xia;Shang Lei;Zheng Yijiao(School of Medicine and Life Sciences,University of Jinan-Shandong Academy of Medical Sciences,Jinan 250062,China;Shandong Academy of Occupational Health and Occupational Medicine,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250062,China)

机构地区：[1]济南大学山东省医学科学院医学与生命科学学院,250062 [2]山东省职业卫生与职业病防治研究院,山东第一医科大学(山东省医学科学院),济南250062

出　　处：《中华劳动卫生职业病杂志》2020年第1期13-19,共7页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：山东省医学科学院院级科技计划(2017-28);山东省医药卫生科技发展计划项目(2017WS711、2018WS171)。

摘　　要：目的探究汞致肾病综合征大鼠肾损伤与细胞凋亡的关系,分析其可能的发病机制。方法将48只健康雄性SPF级BN(Brown-Norway)大鼠采用随机数字表法分成对照组和染毒组,染毒组分别于第1、3、5、7、11、13天以1 mg/kg体重腹部皮下注射HgCl2(1mg/ml)造成肾病综合征模型,对照组注射与染毒组等体积的NaCl。于第14、21、28、35天处死部分大鼠,进行血清肾损伤指标尿素氮(BUN)、肌酐(CRE)的检测,肾组织汞含量检测;原位末端转移酶标记技术(TUNEL)检测细胞凋亡,免疫荧光检测细胞色素C(Cyt C)含量,蛋白免疫印迹法(Western blot)检测线粒体通路凋亡相关蛋白[B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(BAX)、半胱氨酸蛋白酶3(Caspase 3)]、丝裂原活化蛋白激酶(MAPK)信号通路相关蛋白[p38MAPK、细胞外调节蛋白激酶(ERK)]的表达。结果与对照组比较,染毒组7、21、28 d大鼠血清中BUN含量明显增加,21d CRE含量明显增加,28、35 d CRE含量明显降低,14~35 d脏器系数和肾汞含量明显升高,差异均有统计学意义(P<0.05)。与对照组比较,染毒组14~35 d大鼠均出现肾小球基质增多、肾小管扩张等病变及明显的肾细胞凋亡,染毒组14、21 d大鼠肾细胞Cyt C表达明显,多位于肾小管。与对照组比较,染毒组21 d大鼠BAX含量明显升高,14、21 d大鼠Caspase 3含量明显升高,35 d大鼠p38 MAPK含量明显升高,差异均有统计学意义(P<0.05)。结论HgCl2可能通过细胞凋亡的线粒体通路致肾细胞损伤,并引起肾病综合征,而MAPK信号通路可能调控该过程,发挥抑制凋亡作用。Objective To investigate the relationship between renal injury and apoptosis in rats with nephrotic syndrome induced by mercury,in order to find out the pathogenesis.Methods Forty-eight healthy male SPF-grade BN(Brown-Norway)rats were divided into the control group and the exposure group by random number table.The nephrotic syndrome was caused by subcutaneous injection of HgCl2(1 mg/ml)in the abdominal weight per kg of body weight.The control group was injected with the same volume of NaCl as the exposure group.Some rats were sacrificed on the 14th,21st,28th,and 35th days,and the serum kidney injury indicators creatinine(CRE)and urea nitrogen(BUN)were detected,and the renal tissue mercury content was detected;the in situ terminal transferase labeling technology(TUNEL)was detected Apoptosis,immunofluorescence detection of Cyt C content,Western blot detection of mitochondrial pathway apoptosis-related proteins[B-cell lymphoma 2(Bcl-2),Bcl-2 related X protein(BAX),cysteine proteinase 3(Caspase 3)],mitogen-activated protein kinase(MAPK)signaling pathway-related proteins[p38 mitogen-activated protein kinase(P38MAPK),extracellular regulatory protein kinase(ERK)]expression.Results Compared with the control group,the BUN content in the serum of rats in the exposure group was significantly increased on days 7,21,and 28,the CRE content was significantly increased on 21 days,the CRE content was significantly decreased on 28 and 35 days,and the organ coefficient and renal mercury content were 14 to 35 days.Significantly increased,and the differences were statistically significant(P<0.05).Compared with the control group,rats in the exposed group showed increased glomerular stroma,tubule dilatation and other renal cell apoptosis at 14 to 35 days,and Cyt C expression was obvious in the exposed groups at 14,21 days.Compared with the control group,the BAX content of the rats in the exposed group was significantly increased on the 21st day,the content of Caspase 3 in the rats on the 14th and 21st days was significantly increased,a

关 键 词：大鼠 汞中毒 肾病综合征 细胞凋亡 肾损伤 

分 类 号：R692[医药卫生—泌尿科学]