Protective effects and mechanism of echinacoside in sepsis-induced cardiac injury of mice

  AIM  To study the therapeutic effect and protective mechanism of echinacoside (ECH) in myocardial injury in sepsis mice.

  METHODS   C57BL/6 mice were randomly divided into Sham group, CLP group, CLP+ECH group and CLP+ECH+EX527 group. The mouse model of sepsis was established by cecal ligation and perforation, and ECH and SIRT1 selective inhibitor EX527 were intraperitoneally injected. Cardiac systolic function (LVEF and LVFS) and serum myocardial injury markers (LDH and CK-MB) were detected and the degrees of myocardial fibrosis and apoptosis were observed. The expression of NF-κB and production of reactive oxygen species (ROS) were detected. Gene expressions of Collagen I, Collagen III, α-SMA, IL-1α, IL-1β, IL-6, MCP-1, NOX2, NOX4 and protein expressions of cleaved caspase 3 and SIRT1 were determined.

  RESULTS   Compared with those in Sham group, LVEF and LVFS in CLP group were significantly decreased, the serum contents of LDH and CK-MB were significantly increased, the degrees of myocardial fibrosis and apoptosis rate were significantly elevated, and the fluorescence expression of NF-κB and production of ROS in myocardial tissue were significantly increased (all P<0.05). Gene expressions of Collagen I, Collagen III, α-SMA, IL-1α, IL-1β, IL-6, MCP-1, NOX2, NOX4 and protein expression of cleaved caspase 3 were significantly raised (all P<0.05). Meanwhile, protein expression and deacetylation activity of SIRT1 were significantly declined (both P<0.05). Compared with those in CLP group, LVEF and LVFS in CLP+ECH group were significantly increased, the serum contents of LDH and CK-MB were significantly decreased, the degrees of myocardial fibrosis and apoptosis rate were significantly descended and the fluorescence expression of NF-κB and production of ROS in myocardial tissue were significantly reduced (all P<0.01). Gene expressions of Collagen I, Collagen III, α-SMA, IL-1α, IL-1β, IL-6, MCP-1, NOX2, NOX4 and protein expression of cleaved caspase 3 were significantly down-regulated. Meanwhile, the protein expression and deacetylation activity of SIRT1 were significantly increased (P<0.05, P<0.01). The protective effects of ECH on myocardial injury in septic mice were significantly reversed by SIRT1 selective inhibitor EX527 (P<0.05).

  CONCLUSION  Echinacoside inhibits inflammatory response and oxidative stress levels of myocardium by activating the SIRT1 signal, thus alleviating myocardial injury in septic mice.