Study on the Mechanism of Regulating miR-532-3p in Improving Adriamycin Cardiotoxicity with Yiqi Huayu Decoction
Objective To explore the mechanism of regulating miR-532-3p with Yiqi Huayu Decoction to improve adriamycin cardiotoxicity.Methods Totally 25 rats were randomly divided into control group,model group and Yiqi Huayu Decoction low-,medium-and high-dosage groups,with 5 rats in each group.Myocardial injury model was established by intraperitoneal injection of adriamycin 2.5 mg/kg once a week for 8 weeks in model group and Yiqi Huayu Decoction low-,medium-and high-dosage groups.At the same time,Yiqi Huayu Decoction low-,medium-and high-dosage groups were given 2,4,8 g/kg Yiqi Huayu Decoction by gavage respectively,once a day for consecutive 8 weeks.Cardiac function of rats was detected by echocardiography,serum NT-proBNP content was detected by ELISA,morphology of myocardial tissue were observed by HE staining,apoptosis of myocardial tissue was detected by TUNEL staining,miR-532-3p gene expression was detected by RT-qPCR,Western blot was used to detect the expressions of GATA4 and CARP protein.Results Compared with the control group,the left ventricular end systolic diameter(LVESD)and left ventricular end diastolic diameter(LVEDD)of the model group increased significantly,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)significantly decreased(P<0.05),and the serum NT-proBNP content significantly increased(P<0.05),with severe hypertrophy and disordered arrangement of myocardial cells,fibroblast proliferation accompanied by necrosis,and significantly increased apoptosis rate of myocardial cells(P<0.05),the expression of miR-532-3p gene in myocardial tissue significantly increased(P<0.05),and the expressions of GATA4 and CARP proteins in myocardial tissue significantly increased(P<0.05).Compared with the model group,Yiqi Huayu Decoction high-dosage group showed a significant decrease in LVESD and LVEDD(P<0.05),with LVEF and LVFS significantly increased(P<0.05),the content of serum NT-proBNP in Yiqi Huayu Decoction low-,medium-and high-dosage groups were significantly decreased(P<0.05),and myocardial cell damage and fibrosis were improved to varying degrees,the apoptosis rate of myocardial cells was significantly decreased(P<0.05),the expression of miR-532-3p gene in myocardial tissue decreased(P<0.05),and the expressions of GATA4 and CARP proteins in myocardial tissue decreased(P<0.05).Conclusion Yiqi Huayu Decoction can antagonize doxorubicin cardiotoxicity,and its possible mechanism may be related to regulating miR-532-3p to inhibit myocardial fibrosis.