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

作者机构：Dongzhimen HospitalBeijing University of Chinese MedicineBeijing100029China Institute of Radiation MedicineAcademy of Military Medical SciencesBeijing100850China Department of Traditional Chinese MedicineChinese People's Liberation Army General HospitalBeijing100853China 

出 版 物：《Chinese Journal of Integrative Medicine》 (中国结合医学杂志（英文版）)

年 卷 期：2021年第27卷第7期

页      面：542-550页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1005[医学-中医学] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：Supported by the National Basic Research Program(973 Program)of China(No.2012CB518601)。 

主　　题：Chinese medicine mitophagy ischemia-reperfusion injury Parkin ubiquitin 

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-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%,P0.01),a higher apoptotic index(34.33%±2.03%vs.1.81%±0.03%,P0.01),and higher cTnI expression(14.18±1.01 vs.7.96±0.32,P0.01).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,P0.05).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(P0.05).The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group(P0.05).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.