依普利酮下调TNF-α、NF-κB抑制细胞表型转化的研究  

Inhibitory effects of eplerenone on epithelial-mesenchymal transformation via down-regulated TNF-α and NF-κB in rats with unilateral ureteral obstruction

作　　者：梁丽娟[1] 王筝[1] 王蕊[1] 沈正东[1] 李莉[1] 姜国旺[1] 张晓曼[1] 安亚娟[1] 许庆友[1] 

机构地区：[1]河北医科大学中西医结合学院内科教研室,河北石家庄050091

出　　处：《中国药理学通报》2013年第11期1553-1557,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81273684);河北省自然科学基金资助项目(No C2011206042);高等学校博士学科点专项科研基金(No 20111323110008)

摘　　要：目的观察盐皮质激素受体阻断剂依普利酮抑制梗阻性实验动物肾脏细胞表型转化的作用及机制。方法结扎大鼠单侧输尿管(UUO)制备肾间质纤维化动物模型,给予依普利酮100 mg·kg-1·d-1治疗。10 d后摘取肾脏,观察肾脏病理改变。采用Real time-PCR、免疫组化、Western blot方法检测肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)、核转录因子kappa B(NF-κB)、α-平滑肌肌动蛋白(α-SMA)的表达。结果肾脏病理显示,UUO组实验动物肾脏肾小管明显扩张,上皮细胞水肿、坏死,肾间质中有大量炎性细胞浸润,依普利酮可明显减轻其炎症损伤;Real time-PCR、免疫组化、Western blot结果显示,UUO大鼠肾脏TNF-α、NF-κB、α-SMA表达明显增强;依普利酮可下调其表达。结论依普利酮可以通过TNF-α/NF-κB通路,下调炎性介质表达,抑制信号传导,从而抑制细胞的表型转化,减轻肾脏损伤,减缓肾间质纤维化的进展。Aim To observe the effect of mineralocorticoid receptor blockade eplerenone on cell epithelialmesenchymal transformation in obstructed kidney of rats. Methods Renal interstitial fibrotic animals were made with unilateral ureteral obstruction （UUO）and treated with eplerenone 100 mg· kg^-1· d^-1. The kidneys were harvested on the 10th day and tumor necrosis factor-α （TNF-α） , nuclear faetor KB （NF-κB）and α- smooth muscle actin（α-SMA） were detected with Real time-PCR, immunohistochemistry and Western blot. Results Renal pathology showed that edema and necrosis with epithelial cell in kidney with UUO, large numbers of inflammatory cells infiltrated in kidney with renal tubular expansion. The inflammatory injury was inhibited in rats treated with eplerenone significantly. Immunohistochemistry and Western blot showed that expressions of TNF-α, NF -κB and α-SMA were significantly up-regulated with UUO and down-regulated by eplerenone. Couelusion Eplerenone has the role to reduce inflammatory injury and inhibit the cell phenotype transformation by TNF-α/NF-κB pathway.

关 键 词：依普利酮 肾间质纤维化 炎性介质 炎症损伤 TNF-Α NFΚB Α-SMA 

分 类 号：R-332[医药卫生] R322.61