Objective:To explore the mechanism of exercise on improving cardiac fibrosis in heart failure,and the role of miR-378 in regulating Cardiac fibrosis by endurance exercise.Method:Twenty-four SD rats were selected and used transverse aortic constriction(TAC)to replicate the rat model of heart failure with cardiac fibrosis.They were randomly divided into the sham group,the TAC group and the exercise group.The exercise group performed swimming endurance exercise for 6 weeks.After train-ing,the rats in each group were analyzed by echocardiography and pathological morphology,and the serum NT-proBNP concentration was detected by ELISA.Western Blot and qPCR were used to detect the expression of α-SMA,Col Ⅰ,Col Ⅲ,TGF-β1,miR-378,TGF-β1 mRNA,Col1a1,and Col3a1 in heart tissue.Result:Compared with the sham group,left ventricular ejection fraction(LVEF),left ventricular short-axis shortening(LVFS),and output per beat(SV)were significantly decreased(P＜0.05)in TAC group,and there were no significant differences in left ventricular end-diastolic volume(EDV)and left ventricular end-systolic volume(ESV)(P＞0.05),and the serum NT-proBNP concentration was increased significantly(P＜0.01).Patho-logical staining in TAC group showed that cardiomyocytes were obviously edematous and disorganzied,and col-lagen volume fraction(CVF)was significantly increased(P＜0.05);the expression of fibrosis-related factors α-SMA,Col Ⅰ,Col Ⅲ,TGF-β1,TGF-β1 mRNA,Col1a1 and Col3a1 was significantly up-regulated(P＜0.05),and the expression of miR-378 was significantly down-regulated(P＜0.05).Compared with the TAC group,in the Ex group,LVEF,LVFS,SV increased significantly(P＜0.05),LVIDs,ESV decreased significantly(P＜0.01),NT-proBNP concentration decreased(P＜0.05);CVF decreased significantly(P＜0.05).The expressions of Col Ⅰ,Col Ⅲ,Col1a1 and Col3a1 in heart tissues were significantly reduced(P＜0.05),α-SMA was not significantly different,and the expression of miR-378 increased(P＜0.05).The expression of TGF-β1 and mRNA was reduced(P＜0.05).Conclusion:TAC can better replicate the cardiac fibrosis model of pressure-overload heart failure.Endurance exercise can up-regulate miR-378 expression,which can effectively improve the level of cardiac fibrosis,slow down the degree of heart failure,and restore cardiac function.This mechanism of action may be related to the inhibition of cardiac fibroblast activation by exercise-regulated miR-378.

Objective:To explore the mechanism of exercise on improving cardiac fibrosis in heart failure,and the role of miR-378 in regulating Cardiac fibrosis by endurance exercise.Method:Twenty-four SD rats were selected and used transverse aortic constriction(TAC)to replicate the rat model of heart failure with cardiac fibrosis.They were randomly divided into the sham group,the TAC group and the exercise group.The exercise group performed swimming endurance exercise for 6 weeks.After train-ing,the rats in each group were analyzed by echocardiography and pathological morphology,and the serum NT-proBNP concentration was detected by ELISA.Western Blot and qPCR were used to detect the expression of α-SMA,Col Ⅰ,Col Ⅲ,TGF-β1,miR-378,TGF-β1 mRNA,Col1a1,and Col3a1 in heart tissue.Result:Compared with the sham group,left ventricular ejection fraction(LVEF),left ventricular short-axis shortening(LVFS),and output per beat(SV)were significantly decreased(P＜0.05)in TAC group,and there were no significant differences in left ventricular end-diastolic volume(EDV)and left ventricular end-systolic volume(ESV)(P＞0.05),and the serum NT-proBNP concentration was increased significantly(P＜0.01).Patho-logical staining in TAC group showed that cardiomyocytes were obviously edematous and disorganzied,and col-lagen volume fraction(CVF)was significantly increased(P＜0.05);the expression of fibrosis-related factors α-SMA,Col Ⅰ,Col Ⅲ,TGF-β1,TGF-β1 mRNA,Col1a1 and Col3a1 was significantly up-regulated(P＜0.05),and the expression of miR-378 was significantly down-regulated(P＜0.05).Compared with the TAC group,in the Ex group,LVEF,LVFS,SV increased significantly(P＜0.05),LVIDs,ESV decreased significantly(P＜0.01),NT-proBNP concentration decreased(P＜0.05);CVF decreased significantly(P＜0.05).The expressions of Col Ⅰ,Col Ⅲ,Col1a1 and Col3a1 in heart tissues were significantly reduced(P＜0.05),α-SMA was not significantly different,and the expression of miR-378 increased(P＜0.05).The expression of TGF-β1 and mRNA was reduced(P＜0.05).Conclusion:TAC can better replicate the cardiac fibrosis model of pressure-overload heart failure.Endurance exercise can up-regulate miR-378 expression,which can effectively improve the level of cardiac fibrosis,slow down the degree of heart failure,and restore cardiac function.This mechanism of action may be related to the inhibition of cardiac fibroblast activation by exercise-regulated miR-378.

ObjectiveTo observe the difference in the efficacy of three kinds of traditional Chinese medicine （TCM） injections on rat model of heart failure induced by transverse aortic constriction （TAC）， explore the TCM syndrome of the model based on the theory of correspondence of prescription and syndrome， and reveal the biological basis of prescription-syndrome from the perspective of metabolism. MethodRats were treated with TAC for modeling and were divided into Shenmai injection group （6.0 mL·kg^-1）， model group， Danhong injection group （6.0 mL·kg^-1）， Shenfu injection group （6.0 mL·kg^-1） and trimetazidine group （10 mg·kg^-1）， and sham operation group was set up as control. After drug intervention for 15 days， echocardiography， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and myocardial histopathological staining were performed for each group， so as to compare the efficacy to select the effective injection. Colorimetry was used to detect the serum glucolipid metabolism after the intervention of the effective injection， and ultra high performance liquid chromatography-mass spectrometry was used to observe the metabolites and related metabolic pathways in myocardial tissue. ResultCompared with the sham operation group， the left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （FS） in the model group decreased （P<0.01）， while the left ventricular end-diastolic diameter （LVIDd）， left ventricular internal diameter at end-systole （LVIDs） and NT-proBNP level increased （P<0.01）. Compared with model group， LVEF and FS increased （P<0.01）， LVIDd， LVIDs and NT-proBNP level decreased （P<0.05， P<0.01） in Danhong injection group， NT-proBNP level in Shenfu injection group decreased （P<0.05）， LVIDd and NT-proBNP level increased （P<0.05， P<0.01） in Shenmai injection group， in trimetazidine group， LVEF and FS increased （P<0.01）， while LVIDs and NT-proBNP level decreased （P<0.05， P<0.01）. Serum glucose， low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels in Danhong injection group and trimetazidine group were adjusted by callbacks （P<0.01， P<0.05）. There were the callback of 9 myocardial metabolites in Danhong injection group， including glycine， serine and threonine metabolism， glyoxylate and dicarboxylate metabolism， glycerol phospholipid metabolism. There were the callback of 10 myocardial metabolites in trimetazidine group， including glycerol phospholipid metabolism. ConclusionThe efficacy of Danhong injection on heart failure model induced by TAC is significant and superior to Shenfu injection and Shenmai injection， suggesting that the model is closely related to heart-blood stasis. The biological mechanism of Danhong injection interfering with the model involves regulating the metabolic disorder of lipid， glucose， amino acid and butyric acid.