依普利酮下调SGK-1表达抑制梗阻性肾病细胞增殖的研究  

Inhibitory effects of eplerenone on cell proliferation via down-regulated SGK-1 pathway in rats with unilateral ureteral obstruction

作　　者：吴丽敏[1,2] 陈立祥[1] 梁丽娟[1] 王筝[2] 王淼[1] 刘少伟[2] 熊云昭 王萱[1] 许庆友[1,2] 

机构地区：[1]河北医科大学研究生学院,河北石家庄050091 [2]河北中医学院中西医结合学院内科教研室河北省中西医结合肝肾病重点实验室,河北石家庄050091

出　　处：《中国药理学通报》2016年第1期69-73,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81273684;81473652);河北省自然科学基金资助项目(No H2015423009)

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增殖的作用及机制。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,观察大鼠肾脏组织病理改变。采用免疫组化、Western blot方法检测增殖细胞核抗原(PCNA)、血清糖皮质激素诱导蛋白激酶1(SGK-1)、转化生长因子-β1(TGF-β1)的表达。结果肾脏病理显示,UUO组大鼠肾脏有明显的细胞外基质(ECM)积聚,有大量炎性细胞浸润,肾小管扩张明显,上皮细胞脱落,依普利酮可明显减轻其细胞增殖及ECM的沉积;免疫组化和Western blot结果显示,UUO组大鼠肾脏PCNA、SGK-1、TGF-β1表达明显增强;依普利酮可下调其表达。结论依普利酮可通过下调SGK-1的表达,抑制梗阻性肾病细胞增殖,减少ECM的沉积,减缓肾脏纤维化的进程,减轻肾脏损伤。Aim To observe the effect of mineralocorticoid receptor blockade eplerenone on cell proliferation in obstructed kidney of rats. Methods Renal interstitial fibrotic animals were made with unilateral ureteral obstruction( UUO) and treated with eplerenone100 mg· kg- 1· d- 1. The kidneys were harvested on the10 th day and proliferating cell nuclear antigen( PCNA), serum and glucocorticoid induced kinase-1( SGK-1) and transforming growth factor-β1( TGF-β1) were detected with immunohistochemistry and Western blot. Results Renal histopathology showed large quantities extracellular matrix( ECM) accumulation in kidney with UUO,large numbers of inflammato-ry cells infiltrated in renal interstitium,renal tubular expansion and exfoliation of epithelial cells. The cell proliferation and ECM accumulation were inhibited in eplerenone treated rats significantly. Immunohistochemistry and Western blot showed that expressions of PCNA,SGK-1 and TGF-β1were significantly up-regulated with UUO and down-regulated by eplerenone.Conclusion Eplerenone plays the role in inhibiting the cell proliferation and reducing ECM accumulation by down-regulating expression of SGK-1 pathway in rats with unilateral ureteral obstruction.

关 键 词：依普利酮 肾间质纤维化 细胞增殖 UUO PCNA SGK-1 TGF-β1 

分 类 号：R-332[医药卫生] R322.61