Objective

2

To investigate the possible mechanism of

Xinshuaikang Capsule

（心衰康胶囊） in the treatment of heart failure （HF）.

Methods

2

Sixty SD rats were randomly divided into blank group， model group， digoxin group and low-， medium- and high-dose groups of

Xinshuaikang

Capsule

，

with

10 rats in each group. Except for the blank group， rats were intraperitoneally injected with adriamycin for two weeks to establish the HF models. After successful modeling， the blank group and model group were given 1 ml/（100 g·d） of purified water by gavage， while the digoxin group was given 0.02 mg/（kg·d） of digoxin tablet， and the low-， medium- and high-dose groups were respectively given 150， 300， and 450 mg/（kg·d）of

Xinshuaikang

Capsule

by gavage

，

once a day， for 4 consecutive weeks.The changes of cardiac function indicators including left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVEDD）， left ventricular short-axis shortening （LVFS） and left ventricular end-systolic diameter （LVESD） were evaluated by ultrasound diagnostic device. The content of plasma N-terminal B-type natriuretic peptide （NT-proBNP） was detected by ELISA. The expression of sarcoplasmic/endoplasmic reticulum Ca

2+

ATPase 2a （SERCA2a） and miR-25 genes in myocardial tissue was detected by RT-PCR. The expression of SERCA2a protein in myocardial tissue was detected by Western blotting. The pathological changes of myocardial tissue were observed by hematoxylin-eosin （HE） staining.

Results

2

Compared to those in the blank group， LVEF， LVFS， and SERCA2a protein and genes expression in the model group decreased， while LVEDD， LVESD， plasma NT-proBNP， and miR-25 gene expression increased （

P

＜0.05 or

P

＜0.01）； and the structure of the myocardial tissue was severely abnormal in the model group， with obvious hyperplasia of collagen fibers in the interstitial muscle， diffuse distribution of a small amount of inflammatory cells， disorderly arranged and broken myocardial fibers. Compared to those in the model group， LVEF， LVFS， and SERCA2a protein and gene expressions in all three

Xinshuaikang

Capsule

groups and digoxin group increased， while LVEDD， LVESD， plasma NT-proBNP content， and miR-25 expression decreased （

P

＜0.05 or

P

＜0.01）； the pathological damage of myocardial tissue in all intervention groups was improved to a certain extent， and most obvious improvement was seen in the high-dose

Xinshuikang Capsule

group. Digoxin group was superior to all three

Xinshuikang

Capsule

groups in reducing plasma NT-proBNP levels， and with the increase of the dose of

Xinshuikang

Capsule，

NT-proBNP level decreased （

P

＜0.05 or

P

＜0.01）.Compared to those in the medium- and high-dose groups of

Xinshuaikang Capsule

， the expression of SERCA2a protein and gene in the low-dose group decreased， while the expression of miR-25 gene increased （

P

＜0.05）； the expression of SERCA2a protein and gene was lower in the low-dose group than in the high-dose group （

P

＜0.05）.

Conclusion

2

Xinshuaikang Capsule

can improve the myocardial structure and cardiac function of HF rats， and high dose shows best effect. Its mechanism may be related to reducing miR-25 expression and regulating the expression of SERCA2a.