Effect of Yangxinkang Tablets in Regulating Autophagy on  Myocardial Fibrosis in Mice After Chronic Heart Failure

Cui YAN; Zheng ZHOU; Bi-rong LIANG; Ling-jun WANG; Zhong-qi YANG; Shao-xiang XIAN

doi:10.13422/j.cnki.syfjx.20190340

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Effect of Yangxinkang Tablets in Regulating Autophagy on Myocardial Fibrosis in Mice After Chronic Heart Failure

Pharmacology | 更新时间：2021-02-09

- Effect of Yangxinkang Tablets in Regulating Autophagy on Myocardial Fibrosis in Mice After Chronic Heart Failure
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 3, Pages: 53-58(2019)
- 作者机构：
  
  广州中医药大学　第一附属医院，广州　 510405
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190340
  CLC： R289;R541.6+1;R542.2+3
- Received：28 August 2018，
  
  Published Online：16 November 2018，
  
  Published：05 February 2019
- 稿件说明：
移动端阅览
Cui YAN, Zheng ZHOU, Bi-rong LIANG, et al. Effect of Yangxinkang Tablets in Regulating Autophagy on Myocardial Fibrosis in Mice After Chronic Heart Failure[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(3): 53-58.
DOI：

Cui YAN, Zheng ZHOU, Bi-rong LIANG, et al. Effect of Yangxinkang Tablets in Regulating Autophagy on Myocardial Fibrosis in Mice After Chronic Heart Failure[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(3): 53-58. DOI： 10.13422/j.cnki.syfjx.20190340.

摘要

目的:

研究养心康片对心衰后小鼠心肌纤维化的影响，探讨其作用机制。

方法:

采用胸主动脉缩窄法(TAC)建立小鼠慢性心衰模型，建模成功后随机分为假手术组，模型组，3-甲基腺嘌呤(3-MA)组(15 mg·kg

-1

)，养心康片高、中、低剂量组(1 170，585，390 mg·kg

-1

)，假手术组给予等体积蒸馏水灌胃。30 d后行心脏超声检查，收集血流动力学参数；通过心脏石蜡切片，马松(Masson)染色观察心肌细胞形态学变化及心肌纤维化程度；蛋白免疫印迹法(Western blot)检测微管相关蛋白轻链3(LC3)，酵母ATG6同源物(Beclin-1)，溶酶体膜蛋白(LAMP)心肌自噬蛋白，Ⅰ型胶原酶(CollagenⅠ)，Ⅲ型胶原酶(CollagenⅢ)，

-平滑肌肌动蛋白(

-SMA)心肌纤维化标志性蛋白表达情况。

结果:

与假手术组比较，模型组小鼠左心射血分数(LVEF)，短轴缩短分数(FS)明显降低(

0.05)，左心室舒张末期内径(LVDd)，左心室收缩末期内径(LVDs)明显增大(

0.05)，心肌纤维化程度显著加重(

0.01)，

-SMA

CollagenⅠ，CollagenⅢ心肌纤维化标志性蛋白，LAMP

LC3，Beclin-1自噬蛋白表达均明显升高(

0.05)；与模型组比较，3-MA组，养心康高、中剂量组心脏超声各项指标均显著改善(

0.05)，心肌纤维化程度明显改善(

0.01)，

-SMA

CollagenⅠ，CollagenⅢ，LAMP

LC3，Beclin-1表达明显降低(

0.05)，低剂量组心功能、心肌纤维化及各项蛋白表达差异不明显。

结论:

养心康片可通过下调自噬减缓慢性心力衰竭小鼠心肌纤维化，改善心功能。

Abstract

Objective:

To study the effect of Yangxinkang tablets on myocardial fibrosis in mice after heart failure

and to explore its mechanism.

Method:

The model of chronic heart failure in mice was established by thoracic aorta constriction (TAC). After successful modeling

mice were randomly divided into sham operation group

model group

3-methyladenine(3-MA

15 mg·kg

-1

) autophagy inhibitor group

Yangxinkang tablets high

medium

and low dose groups (1 170

585

390 mg·kg

-1

). The sham operation group received equal volume of distilled water. After 30 days

cardiac ultrasound was performed to collect hemodynamic parameters. Cardiac paraffin slices were stained with Masson to observe the morphological changes and fibrosis of cardiomyocytes. Western blot was used to detect lysosome-associated membrane protein(LAMP)

microtubule-associated protein light chain 3 (LC3)

Beclin-1 autophagyportein

-smooth muscle activin(

-SMA )

CollagenⅠ

Collagen Ⅲ protein expression.

Result:

As compared with normal group

the left ventricular ejection fraction (LVEF) and fractional shortening(FS) were significantly decreased(

0.05)

the left ventricular end-diastolic dimension (LVDd) and left ventricular end-systolic dimension (LVDs) were significantly increased (

0.05)

the degree of myocardial fibrosis was significantly aggravated in model group (

0.01)

and the protein expression levels of

-SMA

CollagenⅠ

Collagen Ⅲ

LAMP

LC3

and Beclin-1 were significantly increased in model group (

0.05). As compared with model group

the cardiac ultrasound indexes of the 3-MA group

Yangxinkang high and medium dose groups were significantly improved (

0.05)

the degree of myocardial fibrosis was significantly reduced (

0.01)

the protein expression levels of

-SMA

CollagenⅠ

CollagenⅢ

LAMP

LC3 and Beclin-1 were decreased in 3-MA group

Yangxinkang high and medium dose groups(

0.05)

while the protein expression levels between the model group and Yangxinkang low-dose group showed no significant difference.

Conclusion:

Yangxinkang tablets can reduce myocardial fibrosis and improve cardiac function in mice with heart failure probably by down-regulating autophagy.

关键词

Keywords

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