中国药理学通报2016，Vol.32Issue(3)：337-342,6.DOI:10.3969/j.issn.1001-1978.2016.03.009
2型糖尿病大鼠主动脉Wnt/β-catenin信号通路的变化及SIRT1的调节作用
Alteration of Wnt/β-catenin signaling pathway in type2 diabetic rats’ aorta and regulation of SIRT1
摘要
Abstract
Aim To investigate the alteration of Wnt/β-catenin signaling and sirtuins 1 in type 2 diabetic rats’ aorta and clarify its role in the development of di-abetes aortic disease. Methods The type 2 diabetes rat model was established by injection of streptozocin after five-week of high fat diet. The rats were randomly divided into control group, DM model group of 2 weeks, 4 weeks, 8 weeks and 12 weeks. Fasting blood glucose ( FBG ) , total cholesterol ( TC ) , triglyceride ( TG) , high density lipoprotein-cholesterol( HDL-C) , low density lipoprotein- cholesterol ( LDL-C ) and fast-ing insulin( FINS) levels were tested. HE staining was used to observe the pathological changes of aortal struc-tures. The alteration of Wnt2, β-catenin, TCF4, SIRT1 and sFRP2 in aortawas determined by Western blot and RT-PCR. Results Compared with control group, TC, TG, LDL-C levels of type 2 diabetic rats were significantly increased, HDL-C levels were signif-icantly reduced( P<0. 01 ) . Aortic histological analy-sis revealed that DM induced aortic endothelial cell vacuolar degeneration and necrosis. The expression of Wnt2 and β-catenin level increased significantly in the first 4 weeks of diabetic groups compared to control group, and that in model group of 8 weeks and 12 weeks kept in the high level and showed no significant alteration(P>0. 05). But the expression of TCF4 and SIRT1 was enhanced continuously in DM compared with control group while sFRP2 decreased in the duration of DM development. Conclusions Wnt/β-catenin signa-ling pathway was activated in diabetic aortal injury by regulation of SIRT1 via sFRP2 . Further researches on its mechanism of actionin DM aorta injury may find a new therapeutic target for the disease.关键词
Wnt2/β-catenin/TCF4/SIRT1/sFRP2/2型糖尿病/主动脉损伤Key words
Wnt2/β-catenin/TCF4/SIRT1/sFRP2/type 2 diabetes/aorta injury引用本文复制引用
尹茂山,许淑红,王燕,孙晓慧,梁辰,李杰,牟艳玲..2型糖尿病大鼠主动脉Wnt/β-catenin信号通路的变化及SIRT1的调节作用[J].中国药理学通报,2016,32(3):337-342,6.基金项目
国家自然科学基金资助项目( No 30701022) （ No 30701022）
山东省优秀中青年科学家科研奖励基金计划(No BS2013SW008) （No BS2013SW008）
