Glucocorticoids offer protection against myocardial injury in a murine model of sepsis.

Sepsis is a serious infection-related complication that, in causing significant inflammation, often leads to myocardial injury. Severe inflammation, including in sepsis, is sometimes treated with exogenous glucocorticoids (GCs). Here, to explore the potential effect of GCs to protect against myocardial injury, we created a model of sepsis in rats by performing cecal ligation and puncture (CLP) in 96 rats randomly divided into sham-operated control (N=32), untreated sepsis (CLP, N=32), and GC-treated sepsis (N=32) groups. At 3, 6, 12, and 24 h after surgery, the changes in cardiac hemodynamic indexes, serum inflammatory response factor levels, and myocardial enzymes were measured, along with mitochondrial membrane potential in myocardial cells, apoptosis of myocardial cells, and the expression of nuclear factor kappa B (NF-κB p65) in myocardial tissues. Pathological changes in myocardial cells were also observed. Compared to the sham-operated group, CLP rats experienced deterioration of left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximum rate of left ventricular pressure rise (+dP/dtmax), and the maximum rate of left ventricular pressure drop (-dP/dtmax). CLP rats also had a rise in serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), cardiac troponin I (cTnI), creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and NF-κB p65 in myocardial tissues. The GCs-treated group had lower levels of these inflammatory response molecules than the CLP group, with the exception of anti-inflammatory cytokine interleukin-10 (IL-10), which was higher in the GC-treated rats than the CLP group at each time point post-surgery. Compared to the sham group, CLP rats had a rise in myocardial cell apoptosis and a drop in mitochondrial membrane potential in myocardial cells. In addition, GCs-treated rats had a marked drop in the myocardial cell apoptosis rate and a rise in the mitochondrial membrane potential compared to CLP rats. After intervention with GCs, the pathological changes in heart tissues were also reduced compared to those in the sepsis group. Based on these results, we conclude that exogenous GCs can inhibit a drop in myocardial mitochondrial membrane potential and inhibit myocardial cell apoptosis by blocking the activation of NF-κB, decreasing the generation of proinflammatory cytokines, and relieving inflammatory injury in heart tissues.