Study on Mechanism of Curculigoside Alleviating Myocardial Ischemia-Reperfusion Injury in Rats Based on miR-155/JAK2/STAT3 Signaling Pathway
Objective To investigate the ameliorative effects of curculigoside on myocardial ischemia/reperfusion(I/R)inju-ry in rats and the regulation of microRNA(miR-155)/Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods Sixty rats were randomly divided into sham operation group,model group,curculigoside group,miR-155 overexpression group and miR-155 overexpression+curculigoside group.Except for sham operation group,I/R models were established in other groups through ligation of left anterior descending coronary artery.Six days before modeling,the rats in the curculigoside group and the miR-155 overexpression+curculigoside group were introperitoneally injected with curculigoside(dose 50 mg/kg)once a day.The rats in the miR-155 overexpression group and the miR-155 overexpression+cur-culigoside group were injected with miR-155 mimic at 3 sites in the left ventricle 2 h before modeling.Then 24 h after reperfu-sion,echocardiography was used to detect cardiac function,TTC staining was used to detect myocardial infarction area,qRT-PCR was used to detect mir-155 expression level,and HE staining was used to observe myocardial pathological injury.The ac-tivities of creatine kinase isoenzyme MB(CK-MB),cardiac troponin T(cTnT)and lactate dehydrogenase(LDH)in serum were detected by ELISA,and the relative protein expression levels of p-JAK2 and p-STAT3 were detected by Western blot-ting.Results Compared with the model group,the miR-155 level was decreased,the myocardial infarction area was decreased,LVEF and LVFS were increased,LVESD and LVEDD were decreased,serum levels of CK-MB,cTnT and LDH were decreased and the relative protein expression levels of p-JAK2 and p-STAT3 were increased in curculigoside group,while the changes of a-bove indexes showed an opposite trend in miR-155 overexpression group(P<0.05).Compared with miR-155 overexpression+curculigoside group,miR-155 level was increased,myocardial infarction size was increased,LVEF and LVFS were decreased,LVESD and LVEDD were increased,serum levels of CK-MB,cTnT and LDH were increased and relative protein expressions of p-JAK2 and p-STAT3 were decreased in miR-155 overexpression group.The changes of above indexes showed an opposite trend in curculigoside group(P<0.05).Conclusion Curculigoside can alleviate myocardial injury and improve cardiac function in I/R rats,which may play a role by inhibiting mir-155 expression and up-regulating JAK2/STAT3 signaling pathway.