Protective effect of celastrol on myocardial ischemia-reperfusion injury.
Ключові слова
Анотація
OBJECTIVE
Celastrol, a major active constituent of Tripterygium wilfordii, has antioxidant, anti-inflammatory, and anticancer effects. However, whether celastrol can exert protective effect on myocardial ischemia-reperfusion injury (MIRI) is unknown. The aim of this study was to test the protective effect of celastrol on MIRI and elucidate its underlying mechanism.
METHODS
Cardiomyocytes (H9c2 cells) were subjected to hypoxia for 8 h followed by reoxygenation for 4 h to create hypoxia/reoxygenation (H/R) model, an in vitro MIRI model. Celastrol was added to the medium 60 min before the H/R process . Cell viability was detected using MTT assay. Myocardial injury was evaluated by measuring lactate dehydrogenase (LDH) and creatine kinase MB isoenzyme (CK-MB) activity. Changes in mRNA and protein expression of TNF-α, IL-1ß, and nuclear factor-K B (NF-K B) were measured with RT-qPCR assay and western blot analysis.
RESULTS
Results showed that low-dose celastrol (20 and 50 nM) treatment significantly increased cell viability and decreased LDH and CK-MB activity in the condition of H/R, but high-dose celastrol (200 and 400 nM) resulted in extra injury to cardiomyocytes. Moreover, treatment with 50 nM celastrol significantly downregulated mRNA and protein expression of TNF-α and IL-1ß. Meanwhile, NF-K B mRNA and protein in the nucleus were also correspondingly reduced.
CONCLUSIONS
Our study demonstrated that low-dose celastrol could prevent MIRI in cardiomyocytes by inhibiting the activation of NF-K B, and celastrol may be a potential therapeutic agent for preventing MIRI.
