NF—κB在醛固酮所致大鼠肾损伤中的作用及相关机制  

Role of NF-κB in the progression of aldosterone-induced renal injury and its associated mechanisms

作　　者：杨磊[1] 丁巍[1] 张敏敏[1] 顾勇[1] 

机构地区：[1]复旦大学附属华山医院肾脏科复旦大学附属肾脏病研究所,上海200040

出　　处：《中华肾脏病杂志》2011年第9期673-677,共5页Chinese Journal of Nephrology

基　　金：国家自然科学基金（30900685）

摘　　要：目的探讨NF—κB在醛固酮-1％NaCl诱导的单侧肾切除肾损伤模型中的作用及可能机制。方法32只雄性SD大鼠单侧肾脏切除后随机分为4组：对照组（n=8）；1％NaCl组（1％NaCl饲料喂养，n=8）；醛固酮组（1％NaCl饲料喂养＋0．75μg／h醛固酮泵入，n=8）；吡咯烷二硫氨基甲酸（PDTC）组（1％NaCl饲料喂养＋0．75μg／h醛固酮泵入＋PDTC100mg／kg灌胃，n=8）。共治疗4周。观察各组大鼠收缩压、蛋白尿、肾功能、肾组织形态学改变。Western印迹和实时定量PCR法观察肾皮质胞间黏附分子1（ICAM-1）及结缔组织生长因子（CTGF）的蛋白表达及mRNA表达；EMSA法检测肾皮质NF-κB活性；免疫组化法观察NF-κB的表达情况。结果醛固酮组大鼠表现明显的高血压、蛋白尿、肾小球硬化，ICAM-1及CTGF蛋白和mRNA表达水平较1％NaCl组显著升高（均P〈0．05），NF—κB活性明显增强，NF—κB在肾组织表达也明显增加。PDTC干预后在抑制NF—κB活性和表达的同时，ICAM-1及CTGF表达明显减少（均P〈0．05），同时大鼠血压和肾小球硬化也得到了明显缓解。结论NF—κB抑制剂PDTC可通过减少ICAM-1及CTGF的表达缓解单侧肾切除-1％NaCl-醛固酮所致。肾损伤。Objective To investigate the role of NF-κB in aldosterone-%NaCl-induced renal injury in uninephreetimized SD rats and the potential mechanisms. Methods Thirty-teo male SD rats were uninephrectomized and treated for 4 weeks. Rats were divided into four groups randomly： control group （n=8）, 1%NaCl group （I%NaCI in chow, n=8）, aldosterone group （1% NaCl in chow, 0.75 μg/h aldosterone delayed relase by osmotic mini-pump, SC, n=8）, PDTC group （1%NaCl in chow, 0.75 p,g/h aldosterone, SC, 100 mg/kg PDTC, IG, n=8）. Systolic blood pressure （SBP）, urinary protein, renal function and renal morphologic were observed. The expression of intercellular cell adhesion molecule 1（ICAM-1） and connective tissue growth factor （CTGF） were measured respectively by Western blotting and real-time PCR. The activity and location of NF-κB in renal cortex were detected by electrophoretie mobility shift assay （EMSA） and immunohistochemisty. Results Rats of aldosterone group exhibited higher blood pressure and more serious renal iniury characterized by proteinuria, glomerular sclerosis compared with rats of the 1% NaCl group. Protein and mRNA levels of ICAM-1 and CTGF were significantly increased in aldosterone group rats than those in %NaC] group （all P〈0.05）. Moreover, all these changes were associated with an in,crease in NF-κB activity. Treatment with PDTC which is a specific inhibitor of NF-KB notably alleviated SBP, proteinuria and renal injury in aldosterone-infused rats. Furthermore, PDTC markedly reduced the expression of ICAM-1 and CTGF （all P〈0.05）. Conclusion PDTC can alleviate aldosterone-l%NaCl-induced renal injury in uninephrectimized SD rats by preventing the expression of ICAM-1 and CTGF.

关 键 词：醛固酮 NF—κB 胞间黏附分子1 结缔组织生长因子 

分 类 号：R692[医药卫生—泌尿科学]