Effects of cinnamic acid and its mechanisms on pressure overload⁃induced pathological myocardial hypertrophy in mice

CUI Yimeng; CUI Jingang; DU Xiaoye; XU Jing; CHEN Yu; ZHANG Teng

doi:10.16305/j.1007-1334.2024.2401083

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Effects of cinnamic acid and its mechanisms on pressure overload⁃induced pathological myocardial hypertrophy in mice

更新时间：2024-07-04

- Effects of cinnamic acid and its mechanisms on pressure overload⁃induced pathological myocardial hypertrophy in mice
- Shanghai Journal of Traditional Chinese Medicine Vol. 58, Issue 7, Pages: 58-64(2024)
- 作者机构：
  
  1.上海中医药大学附属岳阳中西医结合医院中西医结合临床研究所（上海 200437）
  2.上海市中医药研究院中西医结合临床研究所（上海 200437）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2024.2401083
  CLC：
- Published：10 July 2024，
  
  Received：19 January 2024，
- 稿件说明：
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崔艺萌,崔金刚,杜霄烨,等.肉桂酸对压力超负荷小鼠病理性心肌肥大的作用及相关机制研究[J].上海中医药杂志,2024,58(7):58-64.

CUI Yimeng,CUI Jingang,DU Xiaoye,et al.Effects of cinnamic acid and its mechanisms on pressure overload⁃induced pathological myocardial hypertrophy in mice[J].Shanghai Journal of Traditional Chinese Medicine,2024,58(7):58-64.
崔艺萌,崔金刚,杜霄烨,等.肉桂酸对压力超负荷小鼠病理性心肌肥大的作用及相关机制研究[J].上海中医药杂志,2024,58(7):58-64. DOI： 10.16305/j.1007-1334.2024.2401083.

CUI Yimeng,CUI Jingang,DU Xiaoye,et al.Effects of cinnamic acid and its mechanisms on pressure overload⁃induced pathological myocardial hypertrophy in mice[J].Shanghai Journal of Traditional Chinese Medicine,2024,58(7):58-64. DOI： 10.16305/j.1007-1334.2024.2401083.

摘要

目的

探讨肉桂酸（CA）对病理性心肌肥大的干预作用，进一步探索其相关机制。

方法

①体内实验：采用主动脉缩窄（TAC）手术构建小鼠心肌肥大模型，将C57BL/6J雄性小鼠随机分为4组，即假手术（Sham）组、模型（TAC）组、CA低剂量（CA-L）组及CA高剂量（CA-H）组。对造模4周后的各组小鼠进行经胸超声心动图分析，评估CA干预对TAC小鼠心脏结构和功能的影响。测算各组小鼠心脏质量指数，采用小麦胚芽凝集素（WGA）染色评估心肌肥大改变。②体外实验：采用苯肾上腺素（PE）诱导H9c2心肌细胞肥大模型，罗丹明-鬼笔环肽和心肌肥大标志物心房利钠肽（ANP）染色评估心肌细胞肥大改变。采用线粒体膜电位（JC-1）检测试剂盒、线粒体超氧化物指示剂（MitoSOX）荧光探针、线粒体通透性转换孔（mPTP）检测试剂盒和增强型三磷酸腺苷（ATP）检测试剂盒评估心肌细胞线粒体功能。

结果

①体内实验：经胸超声心动图分析、心脏质量指数分析和WGA染色结果表明，CA显著抑制TAC诱导的病理性心肌肥大（

0.05）。②体外实验：罗丹明-鬼笔环肽和ANP染色结果表明，CA显著抑制PE诱导的H9c2心肌细胞肥大（

0.05）；JC-1染色结果表明，CA显著抑制PE诱导的心肌细胞线粒体膜电位损伤（

0.05）；MitoSOX荧光探针染色结果表明，CA显著抑制PE诱导心肌细胞线粒体氧化应激水平的增加（

0.05）；mPTP试剂盒分析结果表明，CA显著抑制PE诱导心肌细胞mPTP的开放（

0.05）；增强型ATP检测试剂盒分析结果表明，CA显著抑制PE诱导心肌细胞ATP含量的降低（

0.05）。

结论

CA可有效减轻TAC诱导的病理性心肌肥大，其机制可能部分依赖于对心肌细胞肥大的直接拮抗作用和对线粒体的保护作用。

Abstract

Objective

To investigate the therapeutic effects of cinnamic acid （CA） on pathological myocardial hypertrophy and its underlying mechanisms.

Methods

①

In vivo

experiments were conducted using transverse aortic constriction （TAC） surgery to induce a myocardial hypertrophy model in C57BL/6J male mice， which were randomly divided into four groups： Sham controls， TAC， low-dose CA （CA-L）， and high-dose CA （CA-H） groups. Four weeks after TAC surgery， transthoracic echocardiography was performed to assess the impact of CA on the cardiac structure and function in mice. Cardiac hypertrophy was evaluated by cardiac mass indexes and wheat germ agglutinin （WGA） staining. ②

In vitro

experiments involved using phenylephrine （PE） to induce hypertrophy in H9c2 cardiomyocytes， with rhodamine-phalloidin and atrial natriuretic peptide （ANP） staining assessing cardiomyocyte hypertrophy. Mitochondrial function was assessed using the mitochondrial membrane potential assay kit with JC-1 （JC-1）， red mitochondrial superoxide indicator （MitoSOX） fluorescent probe， mitochondrial permeability transition pore （mPTP） assay kit， and enhanced ATP assay kit.

Results

①

In vivo

experiments demonstrated that CA significantly antagonized TAC-induced pathological myocardial hypertrophy （

0.05）， as

evidenced by transthoracic echocardiography， cardiac mass index， and WGA staining. ②

In vitro

experiment findings： The staining results with rhodamine-phalloidin and ANP indicated that CA significantly suppressed PE-induced hypertrophy in H9c2 cardiomyocytes （

0.05）. JC-1 staining revealed that CA significantly attenuated PE-induced impairment of mitochondrial membrane potential in cardiomyocytes （

0.05）. MitoSOX labeling further revealed that CA significantly mitigated PE-induced increases in mitochondrial superoxide production in H9c2 cardiomyocytes （

0.05）. mPTP assay kit showed that CA significantly attenuated PE-induced mPTP opening in H9c2 cardiomyocytes （

0.05）. Enhanced ATP assay kit indicated that CA significantly prevented the PE-induced reduction in ATP production in cardiomyocytes （

0.05）.

Conclusion

CA effectively mitigates TAC-induced pathological myocardial hypertrophy， possibly through direct antagonistic actions on cardiomyocyte hypertrophy and protective effects on mitochondria.

关键词

心力衰竭病理性心肌肥大肉桂酸线粒体氧化应激小鼠模型作用机制中药研究

Keywords

heart failurepathological myocardial hypertrophycinnamic acidmitochondriaoxidative stressmouse modelmechanism of actiontraditional Chinese herbal medicine research

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