Effect of Oxymatrine on Inflammatory Response in Rats with Myocardial Ischemia-reperfusion
Objective:To investigate the effect of Oxymatrine on the inflammatory response of myocardial ischemia-reperfusion(MIR)rats.Methods:According to the random number table method,144 rats were divided into 6 groups:sham operation group,model group,verapamil(6 mg/kg)group,and Oxymatrine low-dose(25 mg/kg),medium-dose(50 mg/kg),high-dose(100 mg/kg)groups,with 24 rats in each group.The rats were administered by intraperitoneal injection once a day for 7 days before modeling.Thirty minutes after the last administration,the rat left anterior descending coronary artery was blocked for 30 minutes.After reperfusion twenty-four hours,the ST segment changes of the electrocardiogram were observed,the left ventricular systolic pressure(LVSP)and end-diastolic pressure(LVEDP),the maximum rise rate of left ventricular pressure(+dp/dtmax)and the maximum drop rate of left ventricular pressure(-dp/dtmax)were detected by biological function system.The activity of myocardial enzymes[creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH)]in plasma were detected by spectrophotometry.The myocardial infarction rate and myocardial tissue lesions were observed by 2,3,5-triphenyl tetrazolium chloride(TTC)staining and hematoxylin-eosin(HE)staining.The contents of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6]in myocardial tissue were detected by enzyme-linked immunosorbent assay(ELISA),and the expression of Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway proteins and high mobility group box 1(HMGB1)were detected by Western Blot.Results:Oxymatrine pretreatment could significantly reduce ST segment height,LVEDP,myocardial infarction rate,CK-MB,and LDH activities in plasma,TNF-α,IL-1β,IL-6 contents in myocardial tissue,the expression ratio of p-JAK2/JAK2,p-STAT3/STAT3 and the relative expression of HMGB1,and it could significantly increase LVSP,+ dp/dtmax,-dp/dtmax,all of the difference was significant(P<0.05).Oxymatrine pretreatment could significantly improve myocardial tissue lesions.The above effects of Oxymatrine showed certain dose dependence,and the high-dose Oxymatrine group showed the strongest effect.Except for +dp/dtmax and-dp/dtmax,the effects of Oxymatrine high-dose on other indexes were better than those of the verapamil group(P<0.05).Conclusion:Oxymatrine may reduce the inflammatory response in MIR rats by inhibiting the activation of JAK2/STAT3 pathway,and plays protective role on cardiac function in MIR rats.
myocardial ischemia-reperfusionOxymatrineJanus kinase 2/signal transducer and activator of transcription 3 pathwayinflammation responsecardiac functionexeperimental study