Open AccessLycium barbarum polysaccharide protects rats and cardiomyocytes against ischemia/reperfusion injury via Nrf2 activation through autophagy inhibition
Author(s) -
Hào Pān,
Lin Niu,
Yihao Wu,
Liuying Chen,
Xiaowei Zhou,
Yan Zhao
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.12418
Subject(s) - lactate dehydrogenase , reperfusion injury , malondialdehyde , viability assay , apoptosis , troponin complex , creatine kinase , medicine , pharmacology , ischemia , chemistry , troponin i , myocardial infarction , oxidative stress , biochemistry , enzyme
The irreversible loss of cardiomyocytes is mainly the result of ischemic/reperfusion (I/R) myocardial injury, leading to persistent heart dysfunction and heart failure. It has been reported that Lycium barbarum polysaccharide (LBP) has protective effects on cardiomyocytes, but the specific mechanism is still not completely understood. The present study examined the protective role of LBP in myocardial I/R injury. Rats were subjected to myocardial I/R injury and LBP treatment. Moreover, rat myocardial H9C2 cells exposed to hypoxia/reoxygenation (H/R) were used to simulate cardiac injury during myocardial I/R process and were exposed to LBP, rapamycin (an autophagy activator) or nuclear factor‑erythroid factor 2‑related factor 2 (Nrf2) transfection. Morphological examination, histopathological examination and echocardiography were used to determine the cardiac injury after I/R injury. Cell viability and apoptosis were determined via MTT and flow cytometry assays, respectively. The levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin T (cTnT), IL‑1β, IL‑6, TNF‑α, malondialdehyde (MDA) and superoxidase dismutase (SOD) in rat serum, hearts and/or cells were assessed using ELISAs. The expression levels of Beclin 1, LC3II/LC3I, P62 and Nrf2 were analyzed via reverse transcription‑quantitative PCR and western blotting. The results demonstrated that LBP improved heart function and repaired cardiomyocyte damage in I/R model rats, as well as reduced the production of cTnT, CK, LDH, IL‑1β, IL‑6 and TNF‑α. The in vitro study results indicated that LBP increased cell viability, the apoptosis rate, and the levels of SOD and P62, as well as reduced the levels of LDH, CK, IL‑1β, IL‑6, TNF‑α, MDA, Beclin 1 and LC3‑II/LC3‑I in H/R‑injured H9C2 cells. Moreover, LBP promoted Nrf2 nuclear translocation, but decreased Nrf2 expression in the cytoplasm. Rapamycin exacerbated the aforementioned effects in H/R injured H9C2 cells, and partially reversed LBP‑induced effects. Overexpressing Nrf2 counteracted I/R‑induced effects and partially resisted rapamycin‑induced effects. These findings demonstrated that LBP exhibited a cardiac protective effect on the ischemic myocardium of rats after reperfusion and attenuated myocardial I/R injury via autophagy inhibition‑induced Nrf2 activation.