Research of etomidate inhibits myocardial damage after cerebral ischemia-reperfusion in rats through PI3K/AKT/eNOS signaling pathway
Objective To observe the effect of etomidate on myocardial damage after cerebral ischemia-reperfusion in rats and analyze the possible mechanisms.Methods The SD rats were randomly divided into sham-operation group,model group and experimental-L,-M,-H groups,with ten rats per group.The middle cerebral artery occlusion(MCAO)was used to establish cerebral ischemia-reperfusion model rats in model group and experimental-L,-M,-H groups,while the sham-operation group only exposed the middle cerebral artery,but did not block it.At the same time as modeling,experimental-L,-M,-H groups were intraperitoneally injected with 5,15 and 25 mg·kg-1 etomidate,respectively.The sham-operation and model groups were intraperitoneally injected with an equal volume of 0.9％NaCl.Five groups were treated for 14 d with once a day.Enzyme-linked immunosorbent assay was used to detect serum lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CK-MB)levels.Terminaldeoxynucleotidyl-transferase-mediated dUTP nick end labeling method was used to detect myocardial cell apoptosis rate.Western blotting method was used to detect the expression levels of protein kinase B(AKT)and endothelial nitric oxide synthase(eNOS)in myocardial tissue.Results The serum LDH levels of the sham-operation group,model group and experimental-L,-M,-H groups were(186.67±24.89),(289.91±56.26),(257.64±45.13),(226.74±39.82)and(196.43±28.82)U·L-1;the CK-MB levels were(17.81±3.41),(36.89±7.75),(31.18±6.31),(25.21±5.88)and(19.94±4.38)U·L-1;the cardiomyocyte apoptosis rates were(2.99±0.56)％,(13.51±2.37)％,(9.85±1.58)％,(5.92±0.84)％and(3.15±0.81)％;the phosphorylated-AKT/AKT ratios were 0.12±0.02,0.24±0.04,0.39±0.06,0.52±0.07 and 0.97±0.08;the phosphorylated-eNOS/eNOS ratios were 0.09±0.01,0.17±0.04,0.46±0.09,0.77±0.09 and 0.83±0.07.Comparing the model group with the sham-operation group,and comparing the experimental-L,-M,-H groups with the model group,the differences of the above indicators were statistically significant(all P＜0.05).Conclusion Etomidate can reduce myocardial damage after cerebral ischemia-reperfusion in rats,possibly by activating the PI3 K/AKT/eNOS signaling pathway.
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