Effects of Apigenin Regulating Caveolin-1 on Angiotensin 1-7 and Left Ventricular Diastolic Function in Rats with Chronic Heart Failure
Objective:To investigate the effect of apigenin regulating Caveolin-1 on angiotensin 1-7(Ang1-7)and left ventricular diastolic function in rats with chronic heart failure.Methods:According to random number table method,the rats were divided into Sham group,chronic heart failure(CHF)group,apigenin group,Caveolin-1 group and combined group with 10 rats in each group.CHF rat models were established except Sham group.24 h after modeling,the apigenin group rats were intraperitoneally injected 2 mg/kg apigenin,Caveolin-1 group was intraperitoneally injected with 1.2 mg/kg liposome solution of Caveolin-1 plasmid,rats in the combined group were intraperitoneally injected with 2 mg/kg apigenin and 1.2 mg/kg liposome solution of Caveolin-1 plasmid,rats in Sham group and CHF group were intraperitoneally injected with equal volume of normal saline.Cardiac systolic and diastolic function indexes and serum factor levels were compared among all groups.Hematoxylin-eosin(HE)staining was used to detect the pathological morphology of myocardium.The ultrastructure of atrium was observed by electron microscope.Myocardial angiogenesis was detected by protein immunohistochemistry.The protein levels of hypoxia-inducing factor 1(HIF-1),Caveolin-1,vascular endothelial growth factor(VEGF)were detected by Western Blot.Results:Compared with Sham group,left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),Ang1-7,Caveolin-1,HIF-1,VEGF,and vascular number decreased in CHF group(P<0.05).Compared with Sham group,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),angiotensin Ⅱ(AngⅡ),aldosterone(ALD)and renin activity(PRA)increased in CHF group(P<0.05).Compared with CHF group,LVEF,LVFS,Ang1-7,Caveolin-1,HIF-1,VEGF,and the number of blood vessels in apigenin group and Caveolin-1 group increased,LVESD,LVEDD,LVEDV,LVESV,AngⅡ,ALD and PRA decreased(P<0.05).There were no significant differences between apigenin group and Caveolin-1 group(P>0.05).Compared with apigenin group,combined group and Caveolin-1 group,there were statistically significant differences in all indexes(P<0.05).Conclusion:Apigenin can improve cardiac diastolic and systolic functions in rats with chronic heart failure,and can improve myocardial remodeling and protect the heart by upregulating Ang1-7.The mechanism may be related to the activation of Caveolin-1 expression and the increase of myocardial angiogenesis.
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