甘草苷抑制急性心肌梗死大鼠心肌细胞铁死亡的作用研究OACSTPCD

Objective To investigate the effect of liquiritin on ferroptosis of myocardial cells of rats with acute myocardial infarction(AMI)and its corresponding regulatory mechanism.Methods In vivo animal experiment:the rats were divided into sham operation group(0.9％sodium chloride solution),AMI model group(intragastric administration of 0.9％sodium chloride solution after modeling),low-dose liquiritin group(40 mg/kg liquiritin by gavage after modeling)and high-dose liquiritin group(80 mg/kg liquiritin by gavage after modeling)according to the random number table method,with 6 rats in each group.Except for the sham operation group,the other three groups were ligated at the position of 2 mm from the lower end of the left atrial appendage to the left anterior descending branch of the coronary artery in order to construct the AMI rat models.The changes of myocardial ischemia area,histopathological changes,myocardial injury biomarker levels[serum creatine kinase(CK),creatine kinase isoenzyme(CK-MB),and cardiac troponin I(cTnI)],ferroptosis biomarkers levels[reactive oxygen species(ROS),glutathione(GSH),Fe2+,and malondialdehyde(MDA)],and the expression levels of silent information regulator 3(SIRT3),glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)proteins were detected and compared among the four groups after 7 days of administration.In vitro cell experiment:the cultured H9c2 cells were divided into blank group,model group,low-dose liquiritin group(40 µmol/L liquiritin),high-dose liquiritin group(80 μmol/L liquiritin),high-dose liquiritin+Erastin group(80 µmol/L liquiritin+5 μmol/L Erastin),high-dose liquiritin+si-NC group(80 µmol/L liquiritin+0.8 µg si-NC),and high-dose liquiritin+si-SIRT3 group(80 µmol/L liquiritin+0.8 μg si-SIRT3).Except for the blank group without any treatment,the other five groups were treated with hypoxia(1％O2,5％CO2,and 94％N2)to establish the anoxic cell models.The cell viability,apoptosis rate,the levels of ferroptosis biomarkers of ROS,GSH,Fe2+,and MDA,and the expression levels of SIRT3,GPX4 and SLC7A11 proteins were detected and compared among the six groups.Results The results of in vivo animal experiment showed that compared with the model group,the myocardial tissue damage and infarct size were significantly reduced in both the low-dose liquiritin and high-dose liquiritin groups.In the low-dose liquiritin and high-dose liquiritin groups,the levels of CK,CK-MB,cTnI,MDA,ROS,and Fe2+were decreased,while the expression levels of GSH,SIRT3,GPX4,and SLC7A11 were significantly increased(all P＜0.05).Compared with the model group,the myocardial tissue structure and the above indexes in the low-and high-dose liquiritin groups were significantly improved in a dose-dependent manner(all P＜0.05).The results of in vitro cell experiment showed that compared with the model group,the cell activity,GSH,SIRT3,GPX4 and SLC7A11 protein expression levels in the low-dose liquiritin and high-dose liquiritin groups were significantly increased(all P＜0.05),while the apoptosis rate,MDA,ROS,and Fe2+levels were decreased(all P＜0.05).Compared with the high-dose liquiritin group,the cell viability,GSH,SIRT3,GPX4 and SLC7A11 protein expression levels in the high-dose liquiritin+Erastin group and the high-dose liquiritin+si-SIRT3 group were significantly decreased(all P＜0.05),while the apoptosis rate,MDA,ROS and Fe2+levels were increased(all P＜0.05).Conclusion In the cardiomyocytes of AMI rats,liquiritin reduces ferroptosis by regulating SIRT,thereby protecting cardiomyocytes from injury.