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Int J Mol Med. 2018 Jun;41(6):3509-3516. doi: 10.3892/ijmm.2018.3572. Epub 2018 Mar 15.

Cardioprotective effect of rosuvastatin against isoproterenol-induced myocardial infarction injury in rats.

Author information

1
Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
2
Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

Abstract

Rosuvastatin, a member of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, exerts various pharmacological activities. This study evaluated the cardioprotective effect of rosuvastatin on isoproterenol-induced myocardial infarction injury in rats. A rat model of myocardial infarction injury was induced by isoproterenol (ISO) for 2 consecutive days, rosuvastatin was administered for 8 weeks. The levels of myocardial infarct size, aspartate transaminase (AST), alanine transaminase (ALT), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) activities, as well as malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) activities and reduced glutathione (GSH) concentrations were determined. Hematoxylin and eosin staining was used to observe cardiac histological changes. Interleukin-1β (IL-1β) and IL-18 levels in heart tissues were detected with ELISA kits. The mRNA and protein levels of NOD-like receptor superfamily, pyrin domain containing 3 (NLRP3) inflammasome were measured by qRT-PCR and western blot analysis, respectively. Our results showed that treatment with rosuvastatin reduced myocardial infract area, ameliorated histopathological alterations in myocardium, and decreased activities of myocardial injury marker enzymes in ISO-induced rats. In addition, rosuvastatin remarkably restored ISO-induced elevation of lipid peroxidation and decrease of antioxidants, significantly reduced myocardial pro-inflammatory cytokines concentrations in this animal model. Furthermore, rosuvastatin significantly inhibited the activation of NLRP3 inflammasome in this animal model. This study demonstrates that rosuvastatin significantly alleviates ISO-induced myocardial infarction injury. The mechanism is associated with attenuation of oxidative stress and inflammation, via the inhibition of NLRP3 inflammasome.

PMID:
29568858
DOI:
10.3892/ijmm.2018.3572
[Indexed for MEDLINE]

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