Effect of Apigenin on Cardiomyocyte Apoptosis in Diabetic Cardiomyopathy Rats by Regulating Hippo-YAP Signaling Pathway
Objective:The effect of apigenin(QCS)on cardiomyocyte apoptosis in diabetic cardiomyopathy(DCM)rats by regulating Hippo-YAP signaling pathway.Methods:SD rats were divided into blank control group(CK)group(volume normal saline),Model group(volume normal saline),QCS low dose(QCS-L)group(20 mg/kg QCS),QCS high dose(QCS-H)group(40 mg/kg QCS),QCS-H+Verteporfin(Verteporfin)(Hippo-YAP signaling pathway inhibitor)group(40mg/kg QCS+10 mg/kg Verteporfin),10 rats in each group.Cardiac function,fasting plasma glucose(FPG),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),serum creatine kinase(CK),lactate dehydrogenase(LDH),cardiac troponin Ⅰ(cTnⅠ),superoxide dismutase(SOD),catalase(CAT)and malondialdehyde(MDA)in myocardial tissue were detected.The morphology of myocardial tissue was detected by hematoxylin-eosin(HE)staining.The myocardial cell apoptosis was detected by TUNEL staining.The expression of B cell lymphoma-2(Bcl-2),Yes related protein(YAP),cleaved caspase-3(cleaved caspase-3),Bcl-2 related X protein(Bax)and transcription coactivator(TAZ)in myocardial tissue were detected by Western blot(Western blot).Results:Compared with CK group,the myocardial tissue in Model group was severely damaged,and the heart rate(HR),mean arterial pressure(MAP),left ventricular systolic pressure(LVSP),the activity of SOD and CAT,and the expression of Bcl-2,YAP and TAZ protein were significantly decreased in model group,FPG,FINS,insulin resistance index(HOMA-IR),serum creatine kinase(CK),lactate dehydrogenase(LDH)and cardiac troponin(cTnⅠ)levels,myocardial tissue cell apoptosis rate,MDA content,cleaved caspase-3 and Bax protein expression increased(P<0.05).Compared with Model group,the myocardial tissue morphology of rats in QCS-L group and QCS-H group were significantly improved,HR,MAP,LVSP levels,myocardial tissue SOD and CAT activity,Bcl-2,YAP,TAZ protein levels were increased,FPG,FINS,HOMA-IR levels,serum CK,LDH and cTnⅠ levels,myocardial tissue cell apoptosis rate,MDA content,cleaved caspase-3,Bax protein expression decreased(P<0.05).Verteporfin could alleviate the improvement of QCS on cardiomyocyte apoptosis in DCM rats.Conclusion:QCS can reduce the blood glucose level and myocardial cell apoptosis rate in DCM rats,reduce the degree of oxidative stress and myocardial injury,which may be related to the activation of Hippo-YAP signaling pathway.