Protective Effect Of Edaravone On Myocardial Injury In Rats With Sepsis

Objective This study was designed to investigate the myocardial changes in rats with sepsis, and the intervention effect of edaravone injection and its mechanisms of protection on septic myocardial injury in order to provide evidence for preventing and curing septic myocardial injury in clinical practice.Methods A total of 78 healthy male Sprauge-Dawley (SD) rats were randomly divided into normal group (Norm), sham-operation group (Sham), sepsis group (CLP), edaravone treated group (ED)-further divided into low-dose group (ED1) and high-dose group (ED2), and each with 18 rats except for Norm group (with 6 rats); The latter four groups were further divided into three subgroups for different time points:3,6, and 12 hours. Rats with sepsis were prepared with cecal ligation and puncture (CLP). The dynamic changes of the indexes of myocardial injury were observed at various time points in each group, including cTnⅠin serum and hydroxyl radicals (·OH-), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in myocardium. Pathologic changes in heart tissues were also observed. Statistical analysis was done by SPSS 16.0 statistical software. Frequency distribution of data was examined by the Kolmogorov-Smirnov test. Data, according with normal distribution, was described with mean±standard deviation (x±s). One-way ANOVA was used to analyze the difference among groups. If the difference was statistically significant, further using SNK method (q test) to compare between groups. Use Pearson analysis to test correlation.Results 1.Changes of the serum concentration of cTnⅠwere not significantly different between Norm group and Sham group (P>0.05). Serum concentration of cTnⅠin CLP group was significantly higher at 3h, 6h,12h after CLP than in control groups, but lower than in ED1 and ED2 groups (P<0.01); serum concentration of cTnⅠin ED1 group was higher than in ED2 group (P<0.01), but serum concentration of cTnⅠin ED1 and ED2 group was both higher than in control groups (P<0.01).2.Changes of·OH-, MDA and SOD level in myocardium were not significantly different between Norm group and Sham group (P>0.05). The level of·OH- and MDA began to increase significantly in CLP group at 3h after CLP, but decrease at 12h after CLP in comparison with Norm and Sham groups (P<0.01), while such indexes in ED1 and ED2 were lower than in CLP group, but higher than in Norm and Sham group at 3h,6h,12h after CLP (P<0.01); the level of SOD in ED1 and ED2 was significantly lower than in Norm and Sham group, but higher than in CLP group at 3h,6h, 12h after CLP (P＜0.01); the level of·OH- and MDA in ED1 was higher than in ED2 group, the level of SOD in ED1 was lower than in ED2 group (P<0.01).3.Changes of TNF-αand IL-1βlevel in myocardium were not significantly different between Norm group and Sham group (P >0.05). The level of TNF-αand IL-1βin myocardium increased significantly in CLP group at 6h after CLP, but decreased at 12h after CLP in comparison with Norm and Sham group (P<0.01); the level of TNF-αand IL-1βin ED1 group and ED2 group was lower than in CLP group, but higher than in Norm and Sham group (P<0.01); the level of TNF-αand IL-1βin ED2 group were lower than in ED1 group (P<0.01). 4.Pathologic changes of myocardial tissue in septic rats included edema, congestion in mesenchyma, and inflammatory cells infiltration, no pathological damage was seen in Norm group and Sham group, pathological damage of heart tissue in ED1 group and ED2 group was alleviated evidently.5.There was positive correlation between serum cTnⅠlevel and myocardiac·OH- and MDA level, but negative correlation between serum cTnⅠlevel and myocardiac SOD level (P<0.01); There was positive correlation between serum cTnⅠlevel and myocardiac TNF-αand IL-1βlevel (P＜0.01).Conclusion 1.Edaravone can improve septic myocardial injury, probably through reducing oxidative stress and cytokines.2.High-dose edaravone (6mg/Kg) is more efficient than low-dose edaravone (3mg/Kg) in protecting septic myocardial injury.