| Objective: To investigate the effect of Sugemule-3 Decoction on the expression pathways of mitochondrial fusion proteins Mfn1,OPA1,mitochondrial fission protein DRP-1,and MFF in a rat heart failure model induced by isoproterenol(ISO).Methods: Wistar rats were subcutaneously injected with ISO(10 mg/kg/d)for 7days to establish a rat heart failure model.The ethanol extracts of Sugemule-3 soup of different concentrations were given by gavage for 4 and 7 weeks respectively.The cardiac function indexes such as EF,FS,LVEDd and LVEDs of rats were detected by echocardiography.HE staining and Masson staining were used to observe the changes of rat myocardial tissue.The morphological changes of rat cardiomyocyte mitochondria were observed under electron microscope.Western Blot analysis of mitochondrial apoptosis and the expression of proteins related to mitochondrial dynamics.The experimental data was analyzed by SPSS17.0 software.Results: Echocardiographic testing showed that 70% ethanol extract(E-SD-3)of Sugemule-3 Decoction can increase ISO-induced rat EF(p<0.01)and FS(p<0.05)index values,Decrease LVESd and LVEDd(p<0.05)and other cardiac function indicators,indicating that E-SD-3 can effectively improve the cardiac function of rats with heart failure;HE and Masson staining show: E-SD-3 can alleviate ISO-induced time Myocardial histopathological changes such as edema and myocardial fibrosis;electron microscopy shows: E-SD-3 can improve the morphological changes such as loosening,swelling and fragmentation of cardiomyocyte mitochondria in rats with ISO-induced heart failure;Western Blot shows: given After E-SD-3,it can significantly down-regulate the expression of ISO-induced pro-apoptosis-related proteins Bax,Caspase-3,-7,-9,Cleaved-Parp(P<0.05)and down-regulate the endoplasmic reticulum stress-related protein GRP-78,CHOP(P<0.05),up-regulate the expression of anti-apoptosis-related protein Bcl-2,in addition,E-SD-3 can significantly increase the expression of mitochondrial fusion-related proteins Mfn1,OPA1(P<0.05),and reduce the expression of mitochondrial division-related proteins Fis1,MFF,etc.(P<0.05),indicating E-SD-3 By regulating the unbalanced mitochondrial fusion/division process in rats with heart failure,it changes the morphology of mitochondria,relieves ISO-induced apoptosis of cardiomyocytes and reduces mitochondrial damage.Conclusion: E-SD-3 can improve the cardiac function of rats with heart failure by regulating the expression of mitochondrial fusion/division-related proteins and mitochondrial apoptosis-related proteins. |
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