阿霉素肾病大鼠肾组织P^(65)/Rel-A表达趋势及血管紧张素转换酶抑制剂的干预效应  

Up-regulated NF-κB (P^(65)/Rel-A) mRNA during early stage of adriamycin nephrosis in rats may be improved with angiotensin converting enzyme inhibitor intervention

作　　者：李卫卫[1] 马宏[1] 赵晓华[1] 武艳[1] 李娟[1] 王亚娟[1] 

机构地区：[1]山西医科大学第一临床学院儿科,太原030001

出　　处：《中国药物与临床》2008年第12期959-962,1009,共5页Chinese Remedies & Clinics

基　　金：山西高校科技研究开发基金资助项目(2003103)

摘　　要：目的探讨阿霉素肾病大鼠肾损伤早期,肾组织核转录因子(NF)-κB(P65/Rel-A)表达的趋势及其潜在的病理意义。方法以阿霉素肾病大鼠为实验性肾病模型,于肾病早期第1、2、3周观察大鼠蛋白尿、血生化各指标的变化。采用原位杂交方法检测大鼠肾组织P65/Rel-AmRNA表达的情况,并从时相和组织定位表达的趋势上评价P65/Rel-A表达的相关病理意义。结果阿霉素注射后第1周大鼠即出现明显蛋白尿,于第3周即达大量蛋白尿程度(24h)(123±8)mg,同时血生化各指标趋于增高。肾小管中可见大量蛋白管型,肾间质中可见大量炎性细胞浸润。P65/Rel-AmRNA表达于小管上皮细胞胞质。随病变的进展,其核转位趋势明显增加,阳染信号由胞质转至细胞核,P65表达半定量为第1周(4.0±3.3)%、第2周(34.2±2.4)%、第3周(39.9±6.4)%[对照组分别为:(8.5±0.4)%、(8.7±1.0)%、(8.4±0.9)%)]。提示随病变进展肾组织P65/Rel-AmRNA表达呈上调趋势,与对照组比较,差异有统计学意义(P<0.01)。而血管紧张素转换酶抑制剂(ACEI)治疗组上述变化有明显改善[ACEI治疗组1、2、3周P65分别为:(18.5±3.4)%、(22.8±1.6)%、(26.7±4.9)%]。结论阿霉素肾病早期P65/Rel-AmRNA表达上调,与肾组织病变进展相同步,而给予ACEI有一定的干预治疗效应,间接提示血管紧张素及其受体信号可能参与介导核转录因子的表达和活化。Objective To investigate the changes in NF-κB P^65/Rel-A expression and its potential pathogenic role during the early stage of tubulointerstitial lesions in rats with adrimycin nephritis, and to evaluate the effects of benazepril, an angiotensin converting enzyme inhibitor （ACEI）, on NF-κB P^65/Rel-A expression. Methods Wistar male rats with adrimycin nephrosis were used as experiment models. At weeks 1 to 3 during the early phase of nephrosis, we measured the urinary protein and blood biochemical parameters, and detected P^65/Rel-A mRNA expres- sion by in situ hybridization. Results Proteinuria became detectable at one week after use of adriamycin, aggravated progressively to the highest level at week 3（24 h） （123＋8）mg. This observation was accompanied by deterioration of all parameters related with renal function test. Protein casts in renal tubules and inflammatory infiltration in tubulointersti- tial regions were found in massive quantity. In situ hybridization showed up-regulated P^65/Rel-A mRNA expression in tubulointerstitial regions. Meanwhile, there was a significant trend in P65/ReI-A translocation from cytoplasm into the nuclear, as indicated by increasing positive hybridization signals in the nuclei compared with controls [（4.0±3.3）% vs （8.5±0.4）%] at week 1, [（34.2±2.4）% vs （8.7±1.0）%] at week 2, [（39.9±6.4）% vs （8.4±0.9）%] at week 3（P〈0.01）. However, the trend of expression was weaker in each treated groups, with the semi-quantitative assay of P65 expression in ACEI treated group being （18.5±3.4）%, （22.8±1.6）% and （26.7±4.9）% at weeks 1, 2 and 3 weeks, respectively （P〈0.05）. Conehmion NF-κB （P^65/Rel-A） mRNA expression was shown to be significantly enhanced in parallel with aggravating injures in tubulointerstitial lesions during the early stage of adriamycin nephrosis in young rats. Positive effects with ACEI intervention implied that Ang Ⅱ and Ang Ⅱ receptor system may be involved in the expression and activation of

关 键 词：肾病 NF-κB 血管紧张素转换酶抑制药 

分 类 号：R692[医药卫生—泌尿科学]