%0 Journal Article
%T Minocycline protects against myocardial ischemia/reperfusion injury in rats by upregulating MCPIP1 to inhibit NF-¦ÊB activation
%J -
%D 2019
%R https://doi.org/10.1038/s41401-019-0214-z
%X Minocycline is a tetracycline antibiotic and has been shown to play a protective role in cerebral and myocardial ischemia/reperfusion (I/R). However, the underlying mechanism remains unclear. Herein, we investigated whether monocyte chemotactic protein-induced protein-1 (MCPIP1), a negative regulator of inflammation, was involved in the minocycline-induced cardioprotection in myocardial I/R in vivo and in vitro models. Myocardial ischemia was induced in rats by left anterior descending coronary artery occlusion for 1£¿h and followed by 48£¿h reperfusion. Minocycline was administered prior to ischemia (45£¿mg/kg, ip, BID, for 1£¿d) and over the course of reperfusion (22.5£¿mg/kg, ip, BID, for 2£¿d). Cardiac function and infarct sizes were assessed. Administration of minocycline significantly decreased the infarct size, alleviated myocardial cell damage, elevated left ventricle ejection fraction, and left ventricle fractional shortening following I/R injury along with significantly decreased pro-inflammatory cytokine IL-1¦Â and monocyte chemoattractant protein-1 (MCP-1) levels in heart tissue. H9c2 cardiomyocytes were subjected to oxygen glucose deprivation (OGD) followed by reoxygenation (OGD/R). Pretreatment with minocycline (1£¿50£¿¦Ìmol/L) dose-dependently increased the cell viability and inhibited OGD/R-induced expression of MCP-1 and IL-6. Furthermore, minocycline dose-dependently inhibited nuclear translocation of NF-¦ÊB p65 in H9c2 cells subjected to OGD/R. In both the in vivo and in vitro models, minocycline significantly increased MCPIP1 protein expression; knockdown of MCPIP1 with siRNA in H9c2 cells abolished all the protective effects of minocycline against OGD/R-induced injury. Our results demonstrate that minocycline alleviates myocardial I/R injury via upregulating MCPIP1, then subsequently inhibiting NF-¦ÊB activation and pro-inflammatory cytokine secretion
%U https://www.nature.com/articles/s41401-019-0214-z