Effect Of Wenyang Yiqi Huoxue Recipe On Na⁺-K⁺-ATPase And Ca²⁺-ATPase Gene Expression In Cardiomyocytes Of Rats With Chronic Heart Failure

Objective:To explore the effect of Wenyang Yiqi Huoxue Recipe(温阳益气活血方)on the expression of Na+-K+-ATPase and Ca2+-ATPase in cardiomyocytes of rats with chronic heart failure.Methods:The rat model of chronic heart failure was prepared by subcutaneous multi-point injection of isoproterenol for 14 days.70 rats with successful modeling were randomly divided into model group,western medicine group,high dose group of traditional Chinese medicine(drug content 8.1 mg/mL),medium dose group of traditional Chinese medicine(drug content 4.05 mg/mL)and low dose group of traditional Chinese medicine(drug content 2.025 mg/mL),with 14 rats in each group and 15 rats in the blank group.The western medicine group was treated with captopril tablets 5.3 mg/(kg·d-1)+hydrochlorothiazide tablets 2.6 mg/(kg·d-1)+spironolactone tablets 2.6 mg/(kg·d-1);The blank group and model group were given the same amount of normal saline.After 6 weeks of intervention,the cardiac ultrasound index and myocardial histopathological changes of rats in each group were observed,and the heart mass index(HMI)was calculated;The serum BNP level was detected by ELISA;The activity and expression of Na+-K+-ATPase and Ca2+-ATPase in myocardium were detected by enzyme activity colorimetry,immunohistochemistry and RT-PCR.Results:Compared with the blank group,BNP and HMI in the model group increased significantly(P<0.01);The levels of left ventricular ejection fraction(LVEF)and left ventricular short axis shortening(LVFS)decreased significantly(P<0.01),and the activities of Na+-K+-ATPase and Ca2+-ATPase,protein and gene(mRNA)expression in myocardium decreased significantly(P<0.01);A large number of fibrous edema,loose cytoplasm and light staining can be seen in myocardial tissue;A small amount of cardiomyocyte vacuolar degeneration,tiny circular vacuoles can be seen in the cytoplasm,myocardial fiber dissolution can be seen at the edge of the tissue,which is replaced by proliferative connective tissue,accompanied by a small amount of lymphocyte infiltration.Compared with the model group,the degree of myocardial fiber edema,cytoplasmic porosity,inflammatory infiltration,cell vacuolar degeneration and fibrinolysis in the model rats were improved after drug intervention;The levels of LVEF and LVFS increased significantly(P<0.01),the activities of Na+-K+-ATPase and Ca2+-ATPase,protein and mRNA expression in myocardium increased significantly(P<0.01);and the level of BNP,HMI decreased in the high-dose group(P<0.01,P<0.05).Compared with the high-dose group,the levels of LVEF and LVFS in the low and medium dose groups decreased(P>0.05),Ca2+-ATPase activity decreased(P<0.01,P<0.05),the activities of Na+-K+-ATPase and Ca2+-ATPase,protein and mRNA expression in myocardium decreased(P<0.01,P<0.05),BNP,HMI level increased(P<0.01);Na+-K+-ATPase activity decreased in low-dose group(P<0.05),Na+-K+-ATPase activity decreased in medium-dose group(P>0.05),Overall,the improvement effect of the medium dose group was slightly better than that of the low dose group.In general,there was no significant difference between the high-dose group and the western medicine group,but the improvement effect of the high-dose group was slightly better than that of the western medicine group.Conclusion:Wenyang Yiqi Huoxue recipe may improve the cardiac insufficiency of model rats by regulating the activity and expression of myocardial Na+-K+-ATPase and Ca2+-ATPase,so as to play a role in the treatment of chronic heart failure.