CAJ | 학술논문

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。
목적：탐토아리길륜대단측수뇨관경조대서신간질섬유화적작용급궤제。방법24지자성SD대서수궤분위3조,Sham조、UUO조급aliskiren조,제Sham조외,UUO조급aliskiren조균행좌측수뇨관결찰술。aliskiren조술전1 d개시관위급약,아리길륜50 mg/( kg·d),매일1차,련속2주。술후제14천처사대서,류취경조측신조직행HE염색화Masson염색,광경하관찰각조대서신조직병리변화,면역조화화Western인적검측신조직TGF-β1、Smad2화Smad7단백표체수평。결과아리길륜가명현감경대서신간질염성세포침윤、섬유조직증생급신소관확장화위축。면역조화화Western인적결과균현시：여Sham조상비,UUO조TGF-β1、Smad2표체명현상승,이Smad7표체명현하강(균P<0.05)；여UUO조상비,aliskiren조TGF-β1、Smad2표체명현하강,Smad7표체명현상승(균P<0.05)。결론 TGF-β1/Smad신호통로여신간질섬유화유관,아리길륜가억제신간질섬유화,기궤제가능여하조TGF-β1、Smad2적표체화상조Smad7적표체유관。
Objective To investigate the mechanism of aliskiren on renal interstitial fibrosis in rats exerted unilateral u-reteral 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 under-went left ureteral ligation. Rats in aliskiren group were performed with intragastric administration of aliskiren (50mg/ kg·d) at 1 day 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-β1 and Smad2 was increased significantly,but Smad7was 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.