[1]邱晓霞,李逸朗,梁关凤,等.经典Wnt/β-catenin/TCF7L2信号通路在1型糖尿病心肌病中的作用[J].中国药理学通报,2019,(08):1104-1109.[doi:10.3969/j.issn.1001-1978.2019.08.014]
 QIU Xiao-xia,LI Yi-lang,LIANG Guan-feng,et al.Effect of activated canonical Wnt/β-catenin/TCF7L2 signaling pathway in type 1 diabetic cardiomyopathy[J].Chinese Pharmacological Bulletin,2019,(08):1104-1109.[doi:10.3969/j.issn.1001-1978.2019.08.014]
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经典Wnt/β-catenin/TCF7L2信号通路在1型糖尿病心肌病中的作用()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年08期
页码:
1104-1109
栏目:
论著
出版日期:
2019-08-14

文章信息/Info

Title:
Effect of activated canonical Wnt/β-catenin/TCF7L2 signaling pathway in type 1 diabetic cardiomyopathy
文章编号:
1001-1978(2019)08-1104-06
作者:
邱晓霞12李逸朗12梁关凤12张贵平12罗健东1袁文常2侯 宁12
1.广州医科大学药学院药理学教研室,广东 广州 511436; 2.广州医科大学附属第五医院检验科,广东 广州 510000
Author(s):
QIU Xiao-xia12 LI Yi-lang12 LIANG Guan-feng12 ZHANG Gui-ping12 LUO Jian-dong1 YUAN Wen-chang2 HOU Ning12
1.Dept of Pharmacology, Guangzhou Medical University, Guangzhou 511436, China; 2.Dept of Clinical Lab, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000,China
关键词:
糖尿病 链脲佐菌素 心肌肥厚 Wnt/β-catenin/TCF7L2信号通路 iCRT14 c-Myc Nppa
Keywords:
diabetes streptozotocin cardiac hypertrophy Wnt/β-catenin/TCF7L2 signaling pathway iCRT14 c-Myc Nppa
分类号:
R-332; R329.24; R342.2; R394.2; R542.202.2; R587.2; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.08.014
文献标志码:
A
摘要:
目的 探讨Wnt/β-catenin/TCF7L2信号通路在1型糖尿病小鼠心肌病中的作用。方法 利用7~8周龄♂C57BL/6小鼠腹腔注射链脲佐菌素,建立1型糖尿病模型,糖尿病小鼠成模4周后,随机分为糖尿病组、β-catenin通路抑制剂iCRT14(2.5、5 mg·kg-1)组。连续腹腔给药8周后,HE染色检测心脏细胞形态; 免疫组化及Western blot检测β-catenin、TCF7L2蛋白表达; 荧光定量PCR检测β-catenin、Tcf7l2、Nppa、c-Myc mRNA表达。结果 糖尿病组心肌细胞排列相对紊乱、细胞核大小不规则; Western blot和免疫组化结果显示,糖尿病组小鼠心脏β-catenin、TCF7L2表达升高,心肌细胞核内β-catenin、TCF7L2表达明显增多; qPCR显示,β-catenin/TCF7L2通路下游基因c-Myc、心肌肥大基因Nppa表达上调。iCRT14组小鼠心肌细胞排列相对规则,形态趋于正常; β-catenin、TCF7L2蛋白表达降低,核内表达减少; 肥大基因Nppa、下游基因c-Myc mRNA表达明显减低。结论 Wnt/β-catenin/TCF7L2通路活化在糖尿病心肌病发生、发展中发挥重要作用,β-catenin抑制剂能明显减缓1型糖尿病小鼠心肌病的进程。
Abstract:
Aim To determine the role of Wnt/β-catenin/TCF7L2 pathway in diabetic cardiomyopathy.Methods A model of type 1 diabetes mellitus was established by intraperitoneal injection of streptozotocin(STZ)into 7 or 8-week old C57BL/6 mice.After four weeks, the diabetic animals were divided into three groups with seven to eight in each:diabetes mellitus(DM), diabetes injected with β-catenin inhibitor iCRT14(2.5, 5 mg·kg-1).After continuous intrap-eritoneal administration for 8 weeks, heart samples were stained with HE and examined under light microscopy.Expressions and distributions of β-catenin and TCF7L2 in myocardium were detected by immunohistochemistry.Protein levels of β-catenin, Tcf7l2 were detected by Western blot.mRNA levels of β-catenin, Tcf7l2, Nppa and c-Myc were detected by qPCR.Results The myocardial cells in DM were relatively disordered and the size of the nucleus was irregular.Western blot and immunohistochemistry data showed that the expressions of β-catenin and TCF7L2 in heart with DM increased, while those in nucleus of the cardiomyocytes significantly increased.qPCR showed that the mRNA expression of β-catenin downstream target c-Myc and cardiac hypertrophy marker Nppa were up-regulated.After injection of eight weeks with different iCRT14 doses, the cardiomyocytes were relatively regular; the protein levels of β-catenin and TCF7L2 decreased, and their expressions in nucleus decreased as well; the mRNA levels of Nppa and c-Myc markedly decreased.Conclusions Activation of canonical Wnt/β-catenin/TCF7L2 signaling pathway plays a pivotal role in diabetic cardiomyopathy; iCRT14 significantly improves the phenotype of cardiomyopathy in type 1 diabetic mice.

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备注/Memo

备注/Memo:
收稿日期:2019-03-12,修回日期:2019-04-22
基金项目:国家自然科学基金资助项目(No 81773720,81402928); 广州市科技计划项目(No 201804010490); 广州市教育科研计划项目(No 1201610064)
作者简介:邱晓霞(1995-),女,硕士生,研究方向:糖尿病药理学,E-mail: qiuxiaoxia@outlook.com;
侯 宁(1981-),女,博士,教授,硕士生导师,研究方向:糖尿病药理学,通讯作者,E-mail:houning-2003@163.com
更新日期/Last Update: 2019-08-14