Senegenin Protects against Ischemia-reperfusion Inj ury by Ameliorating Endoplasmic Reticulum Stress in Mice / 华中科技大学学报(医学版)

ABSTRACT

Objective To investigate the protective role of senegenin(SEN)in the mouse ischemia-reperfusion injury and its mechanism.Methods Mice were divided at random into control group(the ligature was placed but not ligated for 225 min),is-chemia-reperfusion model group(the anterior descending coronary artery remained ligated for 45 min and then reperfused for 180 min)and SEN treatment group(30 mg/kg SEN was used 10 min before reperfusion).The myocardial infarct size was meas-ured by using Evans blue-TTC staining.Fluorescence assay was employed to detect the activity of Caspase-1 2 and Caspase-3 to assess the myocardial apoptosis.Western blot was used to detect the expression of two endoplasmic reticulum stress (ERS) markers,GRP78 and CHOP,in infarcted myocardia.Results Compared with the control group,the myocardial infarct size was significantly increased,the activities of Caspase-12 and Caspase-3 were increased by 4.71 fold and 3.37 fold,respectively,and the expression levels of ERS markers GRP78 and CHOP were conspicuously elevated in the ischemia-reperfusion model group.Pretreatment with SEN(30 mg/kg)could significantly reduce the myocardial infarct size,the activities of Caspase-12 and Caspase-3 and the expression levels of GRP78 and CHOP when compared with those in the ischemia-reperfusion model group and there was significant difference between the two groups(P<0.05 or P<0.01).Conclusion SEN can protect against the myocardial ischemia-reperfusion inj ury by ameliorating ERS-mediated myocardial apoptosis in mice.