摘要
目的探讨阿利吉仑对单侧输尿管梗阻大鼠肾间质纤维化的作用及机制。方法 24只雌性SD大鼠随机分为3组,Sham组、UUO组及aliskiren组,除Sham组外,UUO组及aliskiren组均行左侧输尿管结扎术。aliskiren组术前1 d开始灌胃给药,阿利吉伦50 mg/(kg·d),每日1次,连续2周。术后第14天处死大鼠,留取梗阻侧肾组织行HE染色和Masson染色,光镜下观察各组大鼠肾组织病理变化,免疫组化和Western印迹检测肾组织TGF-β1、Smad2和Smad7蛋白表达水平。结果阿利吉仑可明显减轻大鼠肾间质炎性细胞浸润、纤维组织增生及肾小管扩张和萎缩。免疫组化和Western印迹结果均显示:与Sham组相比,UUO组TGF-β1、Smad2表达明显上升,而Smad7表达明显下降(均P<0.05);与UUO组相比,aliskiren组TGF-β1、Smad2表达明显下降,Smad7表达明显上升(均P<0.05)。结论 TGF-β1/Smad信号通路与肾间质纤维化有关,阿利吉仑可抑制肾间质纤维化,其机制可能与下调TGF-β1、Smad2的表达和上调Smad7的表达有关。
Objective To investigate the mechanism of aliskiren on renal interstitial fibrosis in rats exerted unilateral ureteral obstruction. Methods 24 female Sprague-Dawley（ SD） rats were randomly divided into 3 groups： Sham-operated group（ Sham）,UUO group（ UUO） and aliskiren treated group（ aliskiren）. Except for Sham group,the UUO and aliskiren group underwent left ureteral ligation. Rats in aliskiren group were performed with intragastric administration of aliskiren（ 50 mg / kg·d） at 1day before surgery,once per day and lasted for 2 weeks. All rats were sacrificed at 14 days after surgery. The pathological changes of the obstruction renal tissues were examined by HE and Masson staining. Immunohistochemistry and Western blot were applied to detect the protein expression of TGF-β1,Smad2 and Smad7. Results Aliskiren could significantly reduce inflammatory cell infiltration,fibroplasia,the expansion and atrophy of the tubular. Compared with Sham group,the protein expression of TGF-β1and Smad2 was increased significantly,but Smad7 was decreased significantly in UUO group（ all P 〈0. 05）. Compared with UUO group,the protein expression of TGF-β1 and Smad2 was decreased significantly,Smad7 was increased significantly in aliskiren group（ all P 〈0. 05）. Conclusion Aliskiren could relieve the renal interstitial fibrosis and fibrosis,and the mechanism of effects may be related to its down regulation TGF-β1,Smad2 and up regulation Smad7.
出处
《中南医学科学杂志》
CAS
2015年第1期26-30,38,共6页
Medical Science Journal of Central South China
基金
衡阳市科学技术局(2013KS34)
作者简介
通讯作者。E-mail：nhliangyu@163．com．
