ABSTRACT
Objective To investigate the effects of Xinkang recipe on myocardial collagen metabolism in rats with doxorubi-cin-induced heart failure.Methods Male SD rats were randomly divided into sham operation group(sham group),model group, Xinkang group and captopril group.The rat model of heart failure was established by intraperitoneal injection of doxorubi-cin.Distilled water,Xinkang decoction and captopril were respectively administrated to rats by gavage for 35 d.The indexes of ventricular remodeling and cardiac function were measured.Myocardial fibrosis was assessed by Masson's trichrome stai-ning.The expression levels of collagen Ⅰ,collagen Ⅲ,TGF-β1,IκB and p56 were detected in myocardial tissues by Western blotting.Myocardial protein and mRNA levels of matrix metalloproteinase-2(MMP-2),MMP-9,and tissue inhibitor of matrix metalloproteinase-1(TIMP-1)and TIMP-2 were detected by Western blotting and RT-qPCR,respectively.Results The expres-sion levels of collagenⅠand collagen Ⅲ protein,the collagen volume fraction(CVF),and the expression levels of TGF-β1 and p56 protein were significantly increased(P< 0.01),and the expression level of IκB protein was significantly decreased in the model group as compared with the sham group(P<0.05 for all).The myocardial protein and mRNA levels of MMP-2,MMP-9, TIMP-1,and TIMP-2 were significantly higher in the model group than in sham group(P<0.05 or P<0.01).The cardiac out-put(CO),left ventricular fractional shortening(FS),and left ventricular ejection fraction(LVEF)were significantly lower while the left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),and left ventricular mass index (LVMI)were significantly higher in model group than in sham group(P<0.01).Compared with the model group,the expres-sion levels of collagen Ⅰand collagen Ⅲ protein,the CVF and the TGF-β1 and p56 expression levels were significantly decreased and the IκB protein expression was significantly increased in Xinkang and the captopril groups(P<0.05).The myocardial pro-tein and mRNA levels of MMP-2,MMP-9,TIMP-1,and TIMP-2 were significantly lower in Xinkang and captopril groups than in control group(P<0.05 or P<0.01).CO,FS,and LVEF were significantly higher while LVEDV,LVESV,and LVMI were significantly lower in Xinkang and captopril groups than in model group(P<0.01).Conclusion Xinkang recipe can reduce col-lagen deposition in the myocardia of rats with doxorubicin-induced heart failure,attenuate left ventricular remodeling,and im-prove cardiac function,which is associated with the inhibition of the NF-κB-mediated upregulation of TGF-β1.
ABSTRACT
AIM:To investigate the effects of Xinkang recipe on myocardial miR-25-3p expression and sarco-plasmic reticulum calcium ATPase 2a ( SERCA2a) activity in heart failure rats .METHODS:Male SD rats were randomly divided into normal group , sham group , model group , Xinkang recipe group ( Xinkang group ) , and captopril group .The heart failure rat model was induced by intraperitoneal injection of doxorubicin .Distilled water , Xinkang recipe and capto-pril were administrated by gastric gavage for 35 d, respectively .The indexes of cardiac function and plasma level of brain natriuretic peptide (BNP) were measured.The SERCA2a activity was determined by the inorganic phosphorus method . The myocardial protein expression of SERCA 2a and phospholamban ( PLB) was detected by Western blot .The myocardial expression of miR-25-3p was detected by stem-loop RT-qPCR.RESULTS:Cardiac output (CO), left ventricular fraction-al shortening ( LVFS) and left ventricular ejection fraction ( LVEF) in Xinkang group and captopril group were significantly higher while the plasma levels of BNP were significantly lower than those in model group (P<0.01).The myocardial ex-pression levels of miR-25-3p in Xinkang group and captopril group were significantly lower while the myocardial protein le -vels of SERCA2a and PLB were significantly higher than those in model group (P<0.01).The SERCA2a/PLB ratio and SERCA2a activity in Xinkang group were significantly higher than those in model group (P<0.05), and no significant change was observed between captopril group and model group .CONCLUSION:Xinkang recipe therapy may improve car-diac function in heart failure rats , which may be related to inhibiting the expression of miR-25-3p, increasing the SER-CA2a/PLB ratio and enhancing SERCA 2a activity in the myocardium .