title: Polydatin post-treatment alleviates myocardial ischaemia/reperfusion injury by promoting autophagic flux.
abstract: Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation. We noted that PD enhanced autophagy and decreased apoptosis during I/R or hypoxia/reoxygenation (H/R), and this effect was antagonized by co-treatment with adenovirus carrying short hairpin RNA for Beclin 1 and 3-methyladenine (3-MA), an autophagic inhibitor. Compared with vehicle-treated mice, PD-treated mice had a significantly smaller myocardial infarct size (IS) and a higher left ventricular fractional shortening (LVFS) and ejection fraction (EF), whereas these effects were partly reversed by 3-MA. Furthermore, in the PD-treated NRCs, tandem fluorescent mRFP-GFP-LC3 assay showed abundant clearance of autophagosomes with an enhanced autophagic flux, and co-treatment with Bafilomycin A1 (Baf), a lysosomal inhibitor, indicated that PD promoted the degradation of autolysosome. In addition, PD post-treatment reduced mitochondrial membrane potential and cellular reactive oxygen species (ROS) production in NRCs, and these effects were partially blocked by Baf. These findings indicate that PD post-treatment limits myocardial I/R injury by promoting autophagic flux to clear damaged mitochondria to reduce ROS and cell death.
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Yuanna
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Department of Pathophysiology, Southern Medical University, No. 1838, Northern Guangzhou Avenue, 510515 Guangzhou, China.
authors.forename: Guiming
authors.initials: G
authors.lastname: Chen
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Huixiong
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Cardiology, 421 Hospital of Chinese People's Liberation Army, No. 468, Xingang Road, 510318 Guangzhou, China.
authors.forename: Long
authors.initials: L
authors.lastname: Ling
authors.affiliation: Department of Rehabilitation, the Sixth Affiliated Hospital of Sun Yat-Sen University, No. 26, Yuanchun Er Henglu, 510655 Guangzhou, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Song
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Pingzhen
authors.initials: P
authors.lastname: Yang
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Yingfeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China zj_chenaihua@126.com wxb2007wxb@126.com.
authors.forename: Xianbao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, 510515 Guangzhou, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Sino-Japan Collaborative Laboratory for Heart Failure Translating Medicine, Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Middle Gongye Avenue, 510282 Guangzhou, China zj_chenaihua@126.com wxb2007wxb@126.com.
authors.forename: Aihua
authors.initials: A
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D005960:Glucosides / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D005960:Glucosides; D017382:Reactive Oxygen Species; D013267:Stilbenes; C058229:polydatin
keywords: apoptosis; autophagy; ischaemia/reperfusion; mitochondrial function; polydatin