Effect of <italic style="font-style: italic">Kangxian Yixin</italic> Formula on cardiomyocyte apoptosis in mice with dilated cardiomyopathy via regulating mitochondrial dynamics

CHANG Hongbo; WANG Zhentao; WU Hong; ZHANG Huichao; QIANG Yitong

doi:10.3969/j.issn.1006-2157.2023.10.010

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Effect of Kangxian Yixin Formula on cardiomyocyte apoptosis in mice with dilated cardiomyopathy via regulating mitochondrial dynamics

Experimental Studies | 更新时间：2023-11-06

- Effect of Kangxian Yixin Formula on cardiomyocyte apoptosis in mice with dilated cardiomyopathy via regulating mitochondrial dynamics
- Journal of Beijing University of Traditional Chinese Medicine Vol. 46, Issue 10, Pages: 1391-1399(2023)
- 作者机构：
  
  1.河南中医药大学　郑州　450046
  2.河南省中医院
- 作者简介：
  
  CHANG Hongbo, Ph.D., Attending Physician. Henan University of Chinese Medicine, No.156, Jinshui East Road, Zhengdong New District, Zhengzhou 450046. E-mail: hnzy281913220@126.com
- 基金信息：
  
  National Natural Science Foundation of China(82205082);Traditional Chinese Medicine Discipline Construction Project of Characteristic Key Discipline of Henan Province(STG-ZYXKY－2020035);Second Batch of Scientific Research Project of National Traditional Chinese Medicine Clinical Research Base of Henan Provincial Health Commission(2021JDZX2001);Traditional Chinese Medicine Top Talent Training Project of Henan Province(2021－15)
- DOI：10.3969/j.issn.1006-2157.2023.10.010
  CLC： R285.5
- Received：26 April 2023，
  
  Published Online：11 August 2023，
  
  Published：30 October 2023
- 稿件说明：
移动端阅览
CHANG Hongbo, WANG Zhentao, WU Hong, et al. Effect of Kangxian Yixin Formula on cardiomyocyte apoptosis in mice with dilated cardiomyopathy via regulating mitochondrial dynamics[J]. Journal of beijing university of traditional chinese medicine, 2023, 46(10): 1391-1399.
DOI：

CHANG Hongbo, WANG Zhentao, WU Hong, et al. Effect of Kangxian Yixin Formula on cardiomyocyte apoptosis in mice with dilated cardiomyopathy via regulating mitochondrial dynamics[J]. Journal of beijing university of traditional chinese medicine, 2023, 46(10): 1391-1399. DOI： 10.3969/j.issn.1006-2157.2023.10.010.

摘要

目的

探讨抗纤益心方对扩张型心肌病(DCM)小鼠心肌细胞线粒体动力学及细胞凋亡的影响。

方法

40只cTnT

R141W

转基因DCM小鼠按照随机数字表法分为模型组、抗纤益心方低剂量组(2.7 g/kg)、抗纤益心方高剂量组(5.4 g/kg)、卡托普利组(10.1 mg/kg)，每组10只。另设10只C57BL/6J小鼠为正常组，各组小鼠分别灌胃8周。小动物超声仪检测小鼠左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、射血分数(EF)、缩短率(FS)，HE染色观察心肌病理形态，透射电子显微镜观察心肌线粒体超微结构，TUNEL法检测心肌细胞凋亡情况，荧光探针检测心肌组织活性氧(ROS)含量，蛋白质印迹法检测心肌线粒体融合蛋白2(MFN2)、视神经萎缩因子1(OPA1)、发动蛋白相关蛋白1(DRP1)、线粒体分裂蛋白1(FIS1)，以及B细胞淋巴瘤/白血病－2(Bcl－2)、Bcl－2相关X蛋白(Bax)、胱天蛋白酶－3(Caspase－3)蛋白表达。

结果

与正常组比较，模型组小鼠LVESD和LVEDD升高、FS和EF降低(均

0.05)，心肌损伤明显，线粒体排列紊乱、肿胀伴空泡样变化，细胞凋亡增多，ROS含量增加，线粒体融合蛋白MFN2、OPA1及抗凋亡因子Bcl－2表达降低，线粒体分裂蛋白DRP1、FIS1及凋亡因子Bax、Caspase－3表达增加(均

0.05)。与模型组比较，抗纤益心方低、高剂量组LVESD和LVEDD降低、FS和EF增加(均

0.05)，心肌损伤减轻，线粒体排列紊乱与肿胀减轻，细胞凋亡减少，ROS含量降低，Bcl－2、MFN2、OPA1蛋白表达增加，Bax、Caspase－3、DRP1、FIS1蛋白表达降低(均

0.05)。

结论

抗纤益心方能够抑制DCM小鼠心肌细胞凋亡，改善心脏功能，其作用机制可能与调控线粒体动力学平衡相关。

Abstract

Objective

To investigate the effect and mechanism of

Kangxi Yixin

Formula (KYF) on cardiomyocyte mitochondrial dynamics and apoptosis in mice with dilated cardiomyopathy (DCM).

Methods

According to the random number table method

40 cTnT

R141W

transgenic DCM mice were randomly divided into the model group

the KYF low-dose group (2.7 g/kg)

the KYF high-dose group (5.4 g/kg)

and the captopril group (10.1 mg/kg)

with 10 mice per group. Another 10 C57BL/6J mice were set up as the normal group

and each group was administered intragastrically for 8 weeks

respectively. Left ventricular end-diastolic diameter (LVEDD)

left ventricular end-systolic diameter (LVESD)

ejection fraction (EF)

and reduction rate (FS) were determined using a small animal ultrasound instrument. Myocardial pathology was observed by HE staining. The ultrastructure of myocardial mitochondria was observed by transmission electron microscope. Apoptosis of cardiomyocytes was detected by the TUNEL method. The content of ROS was detected using a fluorescent probe. The expression levels of MFN2

OPA1

DRP1

FIS1

Bax

Bcl-2

and Caspase-3 were detected by Western blotting.

Results

Compared with the normal group

LVESD and LVEDD were increased

and FS and EF were decreased in the model group (

0.05)

myocardial injury was obvious

mitochondrial disarrangement and swelling were accompanied by vacuole-like changes

the proportion of apoptotic cells was increased

the content of ROS was increased

the protein expression levels of the mitochondrial fusion proteins MFN2 and OPA1 and the anti-apoptotic factor Bcl-2 were decreased

and the expression levels of the mitochondrial fission proteins DRP1 and FIS1 and apoptotic factors Bax and Caspase-3 were increased (

0.05). Compared with the model group

LVESD and LVEDD were decreased

FS and EF were increased (

0.05)

myocardial injury was alleviated

mitochondrial disarrangement and swelling were alleviated

the proportion of apoptotic cells was reduced

the content of ROS was reduced

the protein expression levels of Bcl-2

MFN2

and OPA1 were increased

and the protein expression levels of Bax

Caspase-3

DRP1

and FIS1 were decreased (

0.05) in the KYF low- and high-dose groups.

Conclusion

KYF inhibits cardiomyocyte apoptosis and improves cardiac function in DCM mice

and its mechanism of action may be related to regulating mitochondrial dynamic balance.

关键词

Keywords

references

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Effect of Kangxian Yixin Formula on cardiomyocyte apoptosis in mice with dilated cardiomyopathy via regulating mitochondrial dynamics

DOI：10.3969/j.issn.1006-2157.2023.10.010

摘要

Abstract

关键词

Keywords

references