Effects of Xinkang recipe on myocardial collagen metabolism in rats with doxorubicin-induced heart failure

Abstract

Objective To investigate the effects of Xinkang recipe on myocardial collagen metabolism in rats with doxorubicin-induced heart failure. Methods The heart failure rat model was induced by intraperitoneal injection of doxorubicin.Male SD rats were randomly divided into the control group(n=10), the model group(n=9), the Xinkang group(n=9)and the captopril group(n=10). Masson′s trichrome staining was used to observe myocardial fibrosis.Western blotting was used to detect of expression of collagen Ⅰ, collagen Ⅲ, TGF-β1, IκB and p56 in myocardium.Myocardial protein and mRNA levels of matrix metalloproteinase-2(MMP-2), MMP-9, tissue inhibitor of matrix metalloproteinase-1(TIMP-1)and TIMP-2 were detected by Western blotting and RT-qPCR, respectively. Results Compared with control group, expression of typeⅠ and type Ⅲ collagen protein significantly increased, and the collagen volume fraction(CVF)significantly increased in the model group(all P<0.01). TGF-β1 and p56 protein expression significantly increased, while IκB protein expression significantly decreased in the model group(all P<0.05). The myocardial protein and mRNA levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 were significantly higher in the model group(P<0.01 or P<0.05). Compared with the model group, expression of collagen Ⅰ and collagen Ⅲ protein significantly decreased, and the CVF significantly reduced in Xinkang group and captopril group(both P<0.01). The TGF-β1 and p56 protein expression significantly decreased, and the IκB protein expression significantly increased in Xinkang group and captopril group(all P<0.05). The levels of protein and mRNA of MMP-2, MMP-9, TIMP-1 and TIMP-2 were significantly lower in Xinkang group and captopril group(P<0.01 or P<0.05). Conclusions Xinkang recipe can reduce collagen deposition in myocardium in rats with doxorubicin-induced heart failure.Down-regulating of TGF-β1 protein expression through the inhibition of NF-κB signal transduction pathway might be a potential mechanism underlying effects of Xinkang recipe. Key words: Xinkang recipe; Heart failure; Myocardium collagen; Nuclear factor kappa B; Transforming growth factor beta 1