Effect of Shenfu Yixin Granules on Mitochondrial Dynamics in Rats with Heart Failure After Myocardial Infarction / 中国实验方剂学杂志

ABSTRACT

ObjectiveTo prepare a rat model of heart failure after myocardial infarction by ligation of the anterior descending branch of the left coronary artery， and to observe the effect of Shenfu Yixin granules on the mitochondrial dynamics of rats with heart failure. MethodFifty SD male rats were randomly taken ten as the sham operation group and the rest as modeling group. The rat model of heart failure after myocardial infarction was prepared by ligation of anterior descending branch of left coronary artery. According to the left ventricular ejection fraction（LVEF） on the 28th day after operation， the model rats were randomly divided into the model group， Shenfu Yixin granule low-dose and high-dose groups（3.011， 15.055 g·kg-1） and sacubitril valsartan sodium group（20.83 mg·kg-1）. Each administration group was gavaged daily with the corresponding dose of drug solution， while the sham operation group and model group were given the same amount of normal saline once a day for 28 days， with 6 rats in each group. Ultrasound was used to detect the cardiac function parameters， rat heart mass and body mass were weighed to calculate the cardiac mass index， enzyme linked immunosorbent assay（ELISA） was used to detect serum brain natriuretic peptide（BNP） and soluble growth stimulation expressed gene 2 protein（sST2） levels. Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of the myocardium. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expression of mitochondrial fusion protein 1/2（Mfn1/2）， optic atrophy protein 1（Opa1）， dynamin-related protein 1（Drp1） and fission protein 1（Fis1）. ResultCompared with the sham operation group， the mRNA and protein expression of LVEF， Mfn1， Mfn2， Opal in the model group decreased（P<0.05）， while BNP， sST2， cardiac mass index， Drp1， Fis1 mRNA and protein levels increased（P<0.05）. Compared with the model group， the expression of LVEF， Mfn1， Mfn2， Opal mRNA and protein increased in Shenfu Yixin granule high-dose and sacubitril valsartan sodium groups（P<0.05）， while BNP， sST2， cardiac mass index， Drp1， Fis1 mRNA and protein levels decreased（P<0.05）. Pathological observation showed that compared with the sham operation group， the model group had disordered arrangement of myocardial cells， inflammatory cell infiltration and myocardial fibrosis. Compared with the model group， the degree of inflammatory cell infiltration， myocardial or interstitial fibrosis was improved and alleviated in all administered groups. ConclusionShenfu Yixin granules can resist heart failure， reduce cardiac mass index， decrease BNP and sST2 contents， and improve cardiac function. Its mechanism may be related to the adjustment of mitochondrial dynamics.