激活素A对糖尿病肾脏病小鼠肾脏β-catenin信号通路调控的实验研究  

Experimental Study on the Regulation of Activin A onβ-catenin Signal Pathway in Mice with Diabetic Nephropathy

作　　者：李泽璇 刘高虹[2] 高艺文 任小军[1] LI Zexuan;LIU Gaohong;GAO Yiwen(Department of Nephrology,Third Hospital of Shanxi Medical University,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Taiyuan,030032)

机构地区：[1]山西医科大学第三医院(山西白求恩医院,山西医学科学院,同济山西医院)肾内科,太原030032 [2]山西省人民医院肾内科,太原030012

出　　处：《中国中西医结合肾病杂志》2024年第4期300-303,I0003,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：山西省科技厅国际科技合作重点研发项目(No.201903D421068);山西省自然科学基金青年项目(No.201901D211518);山西省教育厅(留学基金)项目(No.2020-174);山西省人社厅留学基金项目(No.20210016);山西省人民医院136院内专项基金项目。

摘　　要：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(CollagenⅠ)、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。Objective:To observe the effect of competitive inhibition ofβ-catenin/TCF andβ-catenin/Foxo of activin A(ACT A)downstream signal on renal fibrosis in mice with diabetic nephropathy.Methods:30 mice were randomly divided into control 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 biochemical indexes and renal pathological changes.Immunohistochemical method was used to observe the expression of Collagen I,N-Cadherin and vimentin.Results:Compared with group A,the KW/BW,UACR and the expression of Collagen I,N-cadherin and Vimentin in group B were significantly higher.Compared with group B,the KW/BW,UACR and the expression of Collagen I,N-Cadherin 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-regulated.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 activation ofβ-catenin/TCF.

关 键 词：糖尿病肾脏病 激活素A Β-CATENIN TCF FOXO 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]