中山大学学报（医学科学版）2024，Vol.45Issue(3)：393-411,19.
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
Hyperthyroidism Induces Ventricular Remodeling via Activating β-catenin/FoxO1 in Rat Cardiomyocytes
摘要
Abstract
[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.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Key words
hyperthyroidism/myocardial hypertrophy/β-catenin/FoxO1/cardiomyocyte hypertrophy/MSAB/thyroid hormone分类
医药卫生引用本文复制引用
袁勋,班莉,田松麟,朱秋连,张贵平,覃媛,潘丽,侯宁..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[J].中山大学学报（医学科学版）,2024,45(3):393-411,19.基金项目
广东省自然科学基金(2023A1515010412) （2023A1515010412）
广东省普通高校特色创新项目(2020KTSCX293) （2020KTSCX293）
广州卫生职业技术学院基础医学院潘丽名师工作室项目(MS202202) （MS202202）
