Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System*

Hong-xing YANG; Peng WANG; Ning-ning WANG; Shao-dan LI; Ming-hui YANG

doi:10.1007/s11655-019-3166-8

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Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System*

Original Article | Updated：2021-09-01

- Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System*
- Chinese Journal of Integrative Medicine Vol. 27, Issue 7, Pages: 542-550(2021)
- Affiliations：
  
  1.Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing (100029), China
  2.Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing (100850), China
  3.Department of Traditional Chinese Medicine, Chinese People's Liberation Army General Hospital, Beijing (100853), China
- Author bio：
  
  Prof. YANG Ming-hui, E-mail: shanghanmi@sina.com
- Funds：
- DOI：10.1007/s11655-019-3166-8
  CLC：
- Published：01 July 2021，
  
  Published Online：21 June 2019，
  
  Accepted：14 May 2019
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Hong-xing YANG, Peng WANG, Ning-ning WANG, et al. Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System*. [J]. Chinese Journal of Integrative Medicine 27(7):542-550(2021)
DOI：

Hong-xing YANG, Peng WANG, Ning-ning WANG, et al. Tongxinluo Ameliorates Myocardial Ischemia-Reperfusion Injury Mainly via Activating Parkin-Mediated Mitophagy and Downregulating Ubiquitin-Proteasome System*. [J]. Chinese Journal of Integrative Medicine 27(7):542-550(2021) DOI： 10.1007/s11655-019-3166-8.

摘要

Abstract

Objective:

To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (通心络胶囊

TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI).

Methods:

Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group

MIRI group

low- and high-dose TXL (0.5 and 1 g•kg

-1

•d

-1

respectively) groups

atorvastatin (ATV) group (7.2 g•kg

-1

•d

-1

)

chloroquine (CQ) group (10 g•kg

-1

•d

-1

)

and highdose TXL + CQ group. After pharmacological administration for 7 days

rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting.

Results:

Compared with the sham group

the MIRI group exhibited a larger infarcted area (27.13%±0.01%

0.01)

a higher apoptotic index (34.33%±2.03%

.1.81%±0.03%

0.01)

and higher cTnI expression (14.18±1.01

. 7.96±0.32

0.01). The mitochondrial integrity was damaged in the MIRI group

while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58

. 4.33±1.15

0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (

0.05). The ubiquitin response was significantly downregulated in the high-dose TXL group relative to the MIRI group (

0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL.

Conclusions:

TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

关键词

Keywords

Chinese medicinemitophagyischemia-reperfusion injuryParkinubiquitin

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Department of Cardiology, Dongfang Hospital, the Second Affiliated Hospital of Beijing University of Chinese Medicine

Department of Cardiology,Dongzhimen Hospital, the First Affiliated Hospital of Beijing University of Chinese Medicine

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi University of Chinese Medicine

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Science, Xiamen University

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