甲状腺功能亢进激活心肌细胞β-catenin/FoxO1诱导大鼠心室重构的作用

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中文摘要：[目的]探究甲亢激活心肌细胞β-catenin/FoxO1诱导大鼠心室重构的作用和机制.[方法]通过甲状腺激素(T4 0.1 mg/kg/day;腹腔注射)连续给药30 d构建甲亢诱导心室重构大鼠体内模型.利用β-catenin抑制剂MS-AB(14 mg/kg)同时给药30 d,通过Western-blot检测心肌肥厚主要标志物ANP以及β-catenin、FoxO1等蛋白的表达情况;免疫荧光检测β-catenin、FoxO1的核内外表达及分布情况.利用原代培养的乳鼠心肌细胞,使用甲状腺激素(T3 20 nmol/L)处理心肌细胞24 h构建体外甲亢诱导心肌细胞肥厚模型,利用β-cateninsiRNA(30 nmol/L)转染心肌细胞敲低β-catenin,Western-blot和免疫荧光检测抑制β-catenin对甲亢诱导乳鼠心肌细胞肥厚的影响.[结果]Wnt/β-catenin通路激活后β-catenin入核增多并于细胞核内的转录因子结合发挥转录调控作用.β-catenin在甲亢诱导的大鼠心室重构模型心肌细胞核内表达显著增加,而其经典下游转录因子TCF7l2表达无显著差异.我们的结果显示,MSAB抑制β-catenin明显改善甲亢诱导的大鼠心室重构.进一步研究表明甲亢诱导大鼠心肌肥厚过程中心肌细胞β-catenin/FoxO1表达明显增强,抑制心肌细胞β-catenin/FoxO1改善甲亢诱导大鼠心肌肥厚.[结论]甲亢性心肌肥厚心肌细胞β-catenin/FoxO1活化,抑制β-catenin/FoxO1改善甲状腺激素诱导的心肌细胞肥大.

外文标题：Hyperthyroidism Induces Ventricular Remodeling via Activating β-catenin/FoxO1 in Rat Cardiomyocytes

外文摘要：[Objective]To explore how hyperthyroidism induces ventricular remodeling via activating β-catenin/FoxO1 in rat cardiomyocytes.[Methods]Hyperthyroidism-induced ventricular remodeling rat models were established by intraperitoneal injection of levothyroxine(T4)at 0.1 mg/kg for 30 days.β-catenin inhibitor MSAB(14 mg/kg)was admin-istrated for 30 days.We used western blot to detect the expression of myocardial hypertrophy marker ANP,β-catenin and FoxO1;immunofluorescence to examine the expression and intracellular distribution of β-catenin and FoxO1.Hyperthy-roidism-induced cardiomyocyte hypertrophy rat models were established by treatment of triiodothyronine(T3)into cul-tured primary neonatal rat cardiomyocytes for 24 hours.β-catenin siRNA(30 nmol/L)was used to down-regulate β-catenin expression in cardiomyocytes.Western blot and immunofluorescence were used to analyze the effects of β-catenin inhibition on the hyperthyroidism-induced cardiomyocyte hypertrophy.[Results]Following Wnt/β-catenin activation,β-catenin was found increased nuclear expression,to bind to the nuclear transcriptional factors and regulate the gene ex-pression.β-catenin nuclear expression was significantly increased in the hyperthyroidism-induced ventricular remodeling rats,but no change was found in the expression of typical transcriptional factor TCF7l2.Our results revealed that inhibiting β-catenin by MSAB attenuated the hyperthyroidism-induced rat ventricular remodeling.Further analysis indicated that β-catenin/FoxO1 expression was significantly increased in hyperthyroidism-induced myocardial hypertrophy which could be attenuated by suppressing β-catenin/FoxO1 in cardiomyocytes.[Conclusions]β-catenin/FoxO1 is activated in hyperthy-roidism-induced myocardial hypertrophy and β-catenin/FoxO1 inhibition attenuates hyperthyroidism-induced cardiomyo-cyte hypertrophy.

外文关键词：

hyperthyroidismmyocardial hypertrophyβ-cateninFoxO1cardiomyocyte hypertrophyMSABthyroid hormone

作者：

袁勋、班莉、田松麟、朱秋连、张贵平、覃媛、潘丽、侯宁

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作者单位：

广州医科大学药学院药理学教研室//广州医科大学分子靶标与临床药理学重点实验室,广东广州 511436

广州医科大学附属第五医院,广东广州 510799

广州卫生职业技术学院生理教研室,广东广州 510450

关键词：

甲状腺功能亢进症心肌肥厚 β-连环素叉头盒O1蛋白心肌细胞肥大 MSAB 甲状腺激素

基金：

广东省自然科学基金广东省普通高等学校特色创新项目广州卫生职业技术学院基础医学院潘丽名师工作室项目

项目编号：

2023A15150104122020KTSCX293MS202202

出版年：

2024

DOI：

10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20240515.003

中山大学学报(医学科学版)

中山大学

中山大学学报(医学科学版)

CSTPCD北大核心

影响因子：1.608

ISSN：1672-3554

年,卷(期)：2024.45(3)

参考文献量29