Role of retinoic acid-associated orphan nuclear receptor alpha in myocardial injury in septic mice

  AIM  To investigate the role of retinoic acid-related orphan nuclear receptor alpha (RORα) in inflammatory responses and cardiac function injury to sepsis.

  METHODS  A mouse model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS). Macrophage was stimulated by LPS to establish a septic cell model. Cell transfection and mouse tail vein injections of over-expression plasmids were used to over-express RORα in cells and tissues and to explore the role of RORα in inflammatory responses and myocardial damage mediated by sepsis. The changes of RORα, NF-κB p65 and inflammatory cytokines were detected by real-time quantitative PCR and Western blot. The changes of cardiac function in mice with sepsis were detected by enzyme-linked immunosorbent assay and pathological section

  RESULTS  RORα significantly decreased in LPS-stimulated macrophages (P < 0.05). Over-expression of RORα significantly inhibited the expression of inflammatory cytokines IL-1β and TNF-α in LPS-stimulated macrophages (P < 0.05). Over-expression of RORα significantly inhibited LPS stimulated nuclear translocation of NF-κB p65 in macrophages (P < 0.05). Over-expression of RORα in vivo significantly inhibited the release of inflammatory factors IL-1β and TNF-α in the serum of septic mice, reduced the content of myocardial enzymes LDH and CK-MB in septic mice and improved myocardial pathological damage mediated by sepsis.

  CONCLUSION  RORα can inhibit the inflammatory response of macrophages by inhibiting the nuclear translocation of NF-κB p65, thereby alleviating the inflammatory response and myocardial injury in mice with sepsis.