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

• 作者: YANG Hong-xing WANG Peng WANG Ning-ning LI Shao-dan YANG Ming-hui
• 来源期刊: 中国结合医学杂志（英文版）
• 年，卷（期）: 2021,（7）
• 所属期刊栏目: Original Articles
• 页码范围: 542-550
• 页数: 9页
• 语种: 英文
• DOI: 10.1007/s11655-019-3166-8

摘要

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-repeffusion injury (MIRI).Methods:Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups:sham group,MIRI group,low-and high-dose TXL (0.5and 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 high-dose 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％,P＜0.01),a higher apoptotic index (34.33％ ± 2.03％ vs.1.81％ ± 0.03％,P＜0.01),and higher cTnl expression(14.18± 1.01 vs.7.96±0.32,P＜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 vs.4.33± 1.15,P＜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 (P＜0.05).The ubiquitin response was significantly downregulated in the high-dose TXL group relative to the MIRI group (P＜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.