PDTC抑制阿霉素肾病大鼠转录因子NF-κB、AP-1活性  

The effects of PDTC on abnormal activation of NF-κB and AP-1 in the renal cortex of rats with adriamycin-induced nephrosis

作　　者：赵润民[1] 卢思广[1] 陈瑜[1] 曹长春[1] 夏志强[1] 

机构地区：[1]徐州医学院附属医院儿科,江苏徐州221002

出　　处：《徐州医学院学报》2002年第2期129-133,共5页Acta Academiae Medicinae Xuzhou

摘　　要：目的　探讨肾病综合征 (NS)大鼠肾组织转录因子核因子 -κB(NF -κB)、活化蛋白 - 1(AP - 1)DNA结合活性变化及二硫代氨基甲酸吡咯烷 (PDTC)对其活性的影响。方法　应用凝胶电泳迁移率法 (EMSA)和同位素放射自显影等方法检测 :①阿霉素肾病大鼠模型形成过程的不同时间点NF -κB、AP - 1的DNA结合活性、血液生化指标和尿蛋白排泄量 ;②PDTC治疗对上述指标的影响。结果　①大鼠经尾静脉注射阿霉素后第 7天 2 4h尿蛋白排泄量 (UpV) (mg/ 2 4h)开始升高 ,第 2 1天出现大量蛋白尿、低蛋白血症、高脂血症 ;②注射阿霉素后第 7天肾皮质组织NF -κB活性开始升高 ,第 2 8天达高峰 ,其相对密度值 (RDU)明显高于正常对照组 (P <0 .0 1)。AP - 1活性升高迟于NF -κB ,于第 14天活性明显升高 ,第 2 8天活性最高 ,与正常对照组相比有明显差异 (P <0 .0 1)。③经用抗氧化剂PDTC后NF -κB结合活性明显下降 (P <0 .0 1) ,而AP - 1活性无变化 (P >0 .0 5 )。抗氧化剂治疗不能减少UpV(P >0 .0 5 )。结论　①阿霉素肾病大鼠肾皮质中NF -κB、AP - 1DNA结合活性异常升高。②抗氧化剂PDTC能够抑制NF -κB活性但不能抑制AP - 1活性 ,亦不能减少尿蛋白排泄量。Objective To explore the changes of transcription factors NF-κB and AP-1 and the effects of pyrrolidine dithiocarbamate (PDTC) on them in the cortex of kidney from rats with experimental nephrosis.?Methods By using electrophoretic mobility shift assay (EMSA) and isotopic radioautography, the abilities of NF-κB and AP-1 binding to their DNA sites in the renal cortex of rats 7, 14, 21 and 28 d after a single intravenous injection of adriamycine (ADR) were examined, the biochemistry parameters of rat blood and urine were determined. In a second study, the effects of PDTC on these transcription factors′ DNA binding ability were examined from day 14 to day 30 in these rats.?Results 1. NF-κB DNA-binding ability was significantly increased on day 7 and became maximal on day 28 (P<0.01). AP-1 DNA-binding ability was increased on day 14 and became maximal on day 28 (P<0.01). 2. Treatment with PDTC could decrease NF-κB DNA-binding abilities (P<0.01) in rats with nephrosis , but it had no effects on AP-1 (P>0.05) nor on 24-hour urinary protein excretion (UpV, P>0.05), compared with vehicle-treated ADR rats.?Conclusion 1. NF-κB and AP-1 DNA-binding abilities were abnormally increased in the renal cortex of rats with ADR-induced nephrosis. 2. The antioxidant, PDTC, can decrease NF-κB DNA-binding ability, but has no effect on AP-1 and UpV.

关 键 词：阿霉素 肾霉性 肾病综合征 PDTC 大鼠 抗氧化剂 转录因子 NF-κB AP-1 

分 类 号：R692.5[医药卫生—泌尿科学] R979.1[医药卫生—外科学]