Effects of roflumilast on myocardial injury in rats with acute myocardial infarction
Objective To investigate the therapeutic effect of roflumilast on acute myocardial infarction(AMI)rats and its possible mechanism.Methods Sixty SD male rats were randomly divided into sham operation group,model group(AMI),experimental-L group(AMI+1 mg·kg-1 roflumilast),experimental-H group(AMI+3 mg·kg-1 roflumilast),and positive group(AMI+0.9 mg·kg-1 metoprolol),10 rat in each group.AMI modeling was performed after 10 days of continuous drug intervention,and cardiac function indexes of rats were detected after 7 days of successful modeling.Serum factor was detected by enzyme-linked immunosorbent assay(ELISA);myocardial tissue oxidative stress related indexes were detected by kit;myocardial cell apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL);myocardial tissue protein expression was detected by Western blot.Results The left ventricular ejection fraction(EF)levels of rats in sham operation group,model group,experimental-L group,experimental-H group and positive group were(64.44±3.65)％,(36.12±2.50)％,(41.91±3.92)％,(49.90±2.48)％and(53.28±3.22)％,respectively;creatine kinase-MB(CK-MB)levels were(19.15±0.91),(77.86±5.92),(61.58±4.78),(43.62±4.17)and(39.73±4.08)U·L-1,respectively;the contents of malondialdehyde(MDA)were(2.07±0.23),(4.57±0.15),(3.55±0.32),(2.88±0.27)and(2.46±0.17)nmol·mL-1,respectively;TUNEL positive cell rates in each group were(3.96±0.20)％,(16.56±1.82)％,(14.30±0.80)％,(9.73±1.07)％and(7.80±0.56)％;phosphorylation adenosine monophosphate-activated protein kinase(p-AMPK)protein expression levels were 1.10±0.09,0.34±0.04,0.59±0.06,0.87±0.05 and 0.78±0.09,respectively;silencing information regulatory factor-related enzymes 1(SIRT1)protein were 0.96±0.13,0.33±0.03,0.48±0.06,0.77±0.07 and 0.69±0.06,respectively.Model group compared with sham operation group;experimental-L group,experimental-H group,positive group compared with model group,respectively;experimental-L group compared with experimental-H group;the differences of the above indexes were statistically significant(all P＜0.05).Conclusion Roflumilast may inhibit inflammatory response and oxidative stress by activating AMPK/SIRT1 pathway,alleviate myocardial cell apoptosis and improve cardiac function in AMI rats.
roflumilastacute myocardial infarctionoxidative stressinflammatory responseadenylate activated protein kinase/silencing information regulatory factor-related enzymes 1 signaling pathway
国家科技期刊平台
NSTL
万方数据
维普
