期刊
FRONTIERS IN PHARMACOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.00367
关键词
berberine; myocardial ischemia injury; myocardial reperfusion injury; mitophagy; HIF-1 alpha/BNIP3 pathway
资金
- National Natural Science Foundation of China [U1704167]
- Henan Provincial Science and Technology Project [182102310525, 202102310088, 172102310063]
- Joint Construction Project of Henan Medical Science and Technology Tackling Plan [2018020475]
- Henan Medical Science and Technology Tackling Plan Provincial-ministerial Coconstruction Project [SB201902033]
- Key Scientific Research Projects of Colleges and Universities of Henan Province [20A320086]
Berberine (BBR) has a variety of pharmacological activities and is widely used in Asian countries. However, the clinical application of BBR still lacks scientific basis, what protective mechanism of BBR against myocardial ischemia-reperfusion injury (MIRI). In vitro experiments, BBR pretreatment regulated autophagy-related protein expression, induced cell proliferation and autophagosome formation, and reduced the mitochondrial membrane potential (Delta psi m) increase in H9C2 cells. In vivo experiments, BBR reduced the myocardial infarct size, decreased cardiomyocyte apoptosis, and markedly decreased myocardial enzyme (CK-MB, LDH, and AST) activity-induced I/R. In addition, upon BNIP3 knockdown, the regulatory effects of BBR on the above indicators were weakened both in H9C2 cells and in vivo. Luciferase reporter and ChIP assays indicated that BBR mediated BNIP3 expression by enhancing the binding of HIF-1 alpha to the BNIP3 promoter. BBR protects against myocardial I/R injury by inducing cardiomyocytes proliferation, inhibiting cardiomyocytes apoptosis, and inducing the mitophagy-mediated HIF-1 alpha/BNIP3 pathway. Thus, BBR may serve as a novel therapeutic drug for myocardial I/R injury.
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