Effects of Jianxin Granule on Myocardial Remodeling and CaN/NFATc3 Pathway in Rats with Heart Failure of Qi Deficiency and Blood Stasis
Objective To observe the effects of Jianxin Granule on myocardial remodeling in rats with heart failure of qi deficiency and blood stasis,and to explore the mechanism of Jianxin Granule on calcineurin(CaN)/nuclear factor c3 of activated T cells(NFATc3)pathway.Methods Twenty-four male SD rats were randomly divided into Sham group,model group and intervention group,8 rats in each group.The rats in the model group and intervention group were undergone ligation of the left anterior descending coronary artery,and the heart failure model of qi deficiency and blood stasis was established by starvation and exhaustive swimming.The left anterior descending coronary artery was only threaded without ligation in the Sham group.The rats in intervention group were given Jianxin Granule 3.2 g·kg-1·d-1 by gastrogavage once a day,and rats in Sham group and model group were given 2 mL normal saline by gastrogavage once a day.After 4 weeks intervention,rats hemodynamic parameters including left ventricular peak systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),maximal rate of the increase of left ventricular pressure(+dP/dtmax)and maximal rate of the decrease of left ventricular pressure(-dP/dtmax)were detected by cannulated though the right carotid artery,the heart weight was measured,the heart mass index(HMI)was calculated,and the myocardial tissue was stained by Masson and HE to measure infarct size and myocardial cross-sectional area respectively.Myocardial tissue was collected to detect the activity of CaN.Immunohistochemistry and Western Blot were used to detect calcineurin A subunit(CaNA),calcineurin B subunit(CaNB),nuclear and cytosol NFATc3,β-myosion heavy chain(β-MHC)and B-type natriuretic peptide(BNP).Results The rats in Sham group were generally in good condition,with clear outline and neat arrangement of cardiomyocytes,and a little inflammatory cell infiltration.The rats in the model group were fatigue,lethargy,low mobility,and shortness of breath,the myocardium was severely damaged,the outline of myocardium was blurred and disordered,and a large number of inflammatory cells infiltrated the myocardium.Compared with the model group,the mental state of the intervention group was improved,there was no shortness of breath at rest,the activity was increased,the myocardial morphology was more complete than the model group,the arrangement was relatively orderly,and the infiltration of intercellular inflammatory cells was reduced.Compared with the Sham group,LVSP,+dP/dtmax,-dP/dtmax decreased,LVEDP,myocardial infarct size and cross-sectional area,HMI,the activity of CaN in the myocardial tissue,the expression of β-MHC and BNP,the expression of nuclear NFATc3 and nuclear NFATc3/cytosol NFATc3 increased in the model group(P＜0.05).Compared with the model group,LVSP,+dP/dtmax,-dP/dtmax increased,LVEDP,myocardial infarct size and cross-sectional area,HMI,the activity of CaN in the myocardial tissue,the expression of β-MHC and BNP,the expression of nuclear NFATc3 and nuclear NFATc3/cytosol NFATc3 decreased in the intervention group(P＜0.05).Conclusions Jianxin Granule could improve cardiac function and myocardial remodeling,down-regulating the expression of β-MHC and BNP in heart failure rats with qi deficiency and blood stasis.Its mechanism might be related to inhibiting the activity of CaN in myocardial tissue and down-regulating the nuclear translocation of NFATc3.
Jianxin Granuleqi deficiency and blood stasisheart failuremyocardial remodelingcalcineurin/nuclear factor c3 of activated T cellsChinese herbal compound
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