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Isoliquiritigenin attenuates pathological cardiac hypertrophy via regulating AMPKα in vivo and in vitro
Journal of Molecular Histology ( IF 3.2 ) Pub Date : 2022-07-14 , DOI: 10.1007/s10735-022-10090-w
Meiling Gao 1 , Qiang Cai 2 , Haichao Si 1 , Si Shi 3 , Huixia Wei 4 , Miaomiao Lv 1 , Xiaofan Wang 4 , Tieli Dong 1
Affiliation  

Isoliquiritigenin (ISL) is a type of flavonoid, derived from the root of the legume plant Glycyrrhiza, that has multiple pharmacological properties. However, its role in cardiac remodeling induced by pressure overload has yet to be fully elucidated. Aortic banding (AB) surgery was used to establish a cardiac hypertrophy model in male C57BL/6 mice. Mice were randomly divided into four groups (n = 20 per group) as follows: Sham + vehicle, sham + ISL, AB + vehicle and AB + ISL. ISL was administered to the mice intragastrically for 1 week after the operation. To evaluate the role of ISL in mice challenged with AB, echocardiography, histological analysis and molecular biochemistry examinations were performed. ISL treatment decreased cardiac hypertrophy and improved cardiac dysfunction induced by pressure overload. In addition, ISL decreased the cross-sectional area of cardiomyocytes. Furthermore, ISL reversed the AB-mediated increase in phosphorylated (p-)mTOR and p-ERK protein levels and further increased the protein expression of p-AMP-activated protein kinase (AMPK)α in response to AB, whereas knockout of AMPKα abolished the protective effects of ISL. The present study suggested that ISL could suppress pressure overload-induced cardiac hypertrophy through the activation of AMPKα. Therefore, ISL may serve as a therapeutic target for cardiac remodeling.



中文翻译:

异甘草素通过体内外调控AMPKα减轻病理性心脏肥大

异甘草素 (ISL) 是一种黄酮类化合物,来源于豆科植物甘草的根部,具有多种药理特性。然而,其在压力超负荷诱导的心脏重塑中的作用尚未完全阐明。主动脉束带(AB)手术用于建立雄性 C57BL/6 小鼠心脏肥大模型。将小鼠随机分为四组(每组 n = 20),如下所示:假 + 载体、假 + ISL、AB + 载体和 AB + ISL。术后1周给小鼠灌胃ISL。为了评估 ISL 在受到 AB 攻击的小鼠中的作用,进行了超声心动图、组织学分析和分子生化检查。ISL 治疗可减少心脏肥大并改善由压力超负荷引起的心功能不全。此外,ISL 降低了心肌细胞的横截面积。此外,ISL 逆转了 AB 介导的磷酸化 (p-)mTOR 和 p-ERK 蛋白水平的增加,并进一步增加了响应 AB 的 p-AMP 活化蛋白激酶 (AMPK)α 的蛋白质表达,而 AMPKα 的敲除消除了保护性ISL 的影响。本研究表明,ISL 可以通过激活 AMPKα 来抑制压力超负荷诱导的心脏肥大。因此,ISL 可作为心脏重塑的治疗靶点。

更新日期:2022-07-15
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