Effects of decoction for tonifying spleen and regulating lipid on myocardial fibrosis in rats with heart failure via SIRT3/MnSOD signalling pathway
Objective It is to explore the mechanism of decoction for tonifying spleen and regulating lipid(DTSRL)in improving myocardial fibrosis of heart failure via silent information regulator 3/manganese superoxide dismutase(SIRT3/MnSOD)signal pathway.Methods Seventy male SD rats were selected,in which 10 ones were randomly selected as the normal group,and the remaining 60 rats were given adriamycin by tail vein injection to establish models of myocardial fibro-sis of heart failure.After successful modeling,the surviving rats were randomly divided into model group,captopril group,DTSRL low-dose group,DTSRL medium-dose group,and DTSRL high-dose group,with 10 rats in each group.The capto-pril group was given captopril 2.6 mg/kg by gavage,the low-dose,medium-dose and high-dose groups of DTSRL were giv-en DTSRL 4.38 g/kg,8.75 g/kg and 17.75 g/kg by gavage,respectively,and the normal group and model group were given equal volumes of normal saline by gavage,all once daily,continuously treated for 6 weeks.40 minutes after the final gavage,the cardiac function was assessed by cardiac ultrasound;left ventricular myocardial tissue was taken to observe the pathological morphology and myocardial fibrosis by HE and Masson staining,and the myocardial collagen volume fraction was calculated;the expressions of Collagen Ⅰ,Collagen Ⅲ,SIRT3 and MnSOD proteins in myocardial tissue were detec-ted by Western blot,the expressions of Collagen Ⅰ,Collagen Ⅲ,SIRT3 and MnSOD mRNAs in myocardial tissue were detected by RT-qPCR.Results The LVIDd,LVIDs and myocardial collagen volume fraction of rats in the model group were higher than those of rats in the normal group(all P<0.05),and the LVEF and LVFS were significantly lower than those in the normal group(all P<0.05),with myocardial fiber ruptures and hemorrhages;the LVIDd,LVIDs and myocardial collagen volume fraction of rats in the captopril group and every DTSRL group were lower than those of rats in the model group(all P<0.05),and the LVEF and LVFS were significantly higher than those in the model group(all P<0.05),the myocardial fibrosis was improved,and the improvements were more obvious in the captopril group and the middle-dose and high-dose groups of DTSRL,but a small amount of hemorrhage was still left.The relative expressions of Collagen Ⅰ and Collagen Ⅲ proteins and mRNA in myocardial tissue of rats in the model group were significantly higher than those in the normal group(all P<0.05),and the relative expressions of SIRT3 and MnSOD proteins and mRNA in myocardial tis-sue were significantly lower than those in the normal group(all P<0.05);the relative expressions of Collagen Ⅰ and Col-lagen Ⅲ proteins and mRNA in myocardial tissue of rats in the captopril group and the middle-dose and high-dose groups of DTSRL were significantly lower than those in the model group(all P<0.05),and the relative expressions of SIRT3 and MnSOD proteins and mRNA in myocardial tissue of rats in the captopril group and high-dose group of DTSRL were signifi-cantly higher than those in the normal group(all P<0.05).Conclusion Decoction for tonifying spleen and regulating lipid can relieve oxidative stress and improve myocardial fibrosis of heart failure in rats maybe by activating SIRT3/MnSOD sig-nalling pathway.
heart failuremyocardial fibrosisdecoction for tonifying spleen and regulating lipidsilent information regulator 3manganese superoxide dismutase
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