目的:观察靶向调控激活素A(ACT A)下游β-连环蛋白(β-catenin)/T细胞因子(TCF)与β-catenin/叉头框转录因子-O(Foxo)信号的竞争抑制对糖尿病肾脏病(DKD)小鼠肾脏纤维化的影响.方法:30 只小鼠随机将其分为对照组(A组)、糖尿病组(B组)、ACT A处理组(C组)、ACT A + iCRT3 处理组(D组)和ACT A + iCRT3 + AS1842856 处理组(E组).留取各组小鼠血、尿和肾组织样本,分别检测常规生化指标及肾脏病理改变,采用免疫组织化学法观察小鼠肾脏Ⅰ型胶原蛋白(Collagen Ⅰ)、N-钙黏蛋白(N-Cadherin)和波形蛋白(Vimentin)的表达.结果:与A组小鼠相比,B组小鼠肾脏指数(KW/BW)、尿微量白蛋白/肌酐比值(UACR)明显升高,肾组织Collagen Ⅰ、N-cadherin和Vimentin的表达均增加;与B组小鼠比较,使用ACT A处理的C组小鼠的KW/BW、UACR及肾组织Collagen Ⅰ、N-Cadherin和Vimentin的表达进一步上调;与C组相比,使用TCF阻断剂处理的D组小鼠KW/BW、UACR及肾组织Collagen Ⅰ、N-Cadherin和Vimentin的表达下调;与D组相比,使用TCF和Foxo双重阻断剂处理的E组小鼠上述指标有所上调.结论:ACT A能够通过增强β-catenin/TCF的信号活化,促进糖尿病肾脏病小鼠肾脏纤维化进程.
Experimental Study on the Regulation of Activin A on β-catenin Signal Pathway in Mice with Diabetic Nephropathy
Objective:To observe the effect of competitive inhibition of β-catenin/TCF and β-catenin/Foxo of activin A(ACT A)downstream signal on renal fibrosis in mice with diabetic nephropathy.Methods:30 mice were randomly divided into con-trol group(group A),diabetic group(group B),ACTA treatment group(group C),ACTA +iCRT3 treatment group(group D)and ACTA +iCRT3 +AS1842856 treatment group(group E).Blood,urine and renal tissue samples were taken to detect routine biochem-ical indexes and renal pathological changes.Immunohistochemical method was used to observe the expression of Collagen Ⅰ,N-Cad-herin and vimentin.Results:Compared with group A,the KW/BW,UACR and the expression of Collagen Ⅰ,N-cadherin and Vim-entin in group B were significantly higher.Compared with group B,the KW/BW,UACR and the expression of Collagen Ⅰ,N-Cad-herin and Vimentin in renal tissue were further up-regulated in group C treated with ACTA.Compared with group C,the KW/BW,UACR and the expression of Collagen Ⅰ,N-Cadherin and Vimentin in group D treated with the blocker of the TCF were down-regu-lated.Compared with group D,The above-mentioned indexes of group E mice treated with the blockers of TCF and Foxo were up-regulated.Conclusion:ACTA can promote the process of renal fibrosis in mice with diabetic nephropathy by enhancing the signal acti-vation of β-catenin/TCF.
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